We have studied the relationship between the prolaction (PRL) release induced by thyroliberin (TR... more We have studied the relationship between the prolaction (PRL) release induced by thyroliberin (TRH) and theophylline and the formation and inactivation of adenosine 3', 5'-cyclic monophosphate (cyclic AMP) in cultured rat-pituitary cells (GH3 cells). TRH, which stimulated prolactin release, increased cyclic AMP formation and stimulated transiently both the low- and high-Km cyclic phosphodiesterases. The maximal effect on the phosphodiesterase was observed at 30 mM TRH. The stimulatory effect of TRH on the activity of the cyclic AMP phosphodiesterases was duplicated by incubation of the cells with cyclic AMP (2-10 mM). In washed particulate GH3 cell fractions, TRH increased the adenylyl cyclase activity up to 180%. Treatment of GH3 cells with theophylline stimulated the release of PRL and inhibited cyclic AMP degradation probably leading to the measured increase in cellular concentrations of the nucleotide. The effects of TRH and theophylline on cellular cyclic AMP concentrat...
cyclicCHAD is a peptide representing the α2β1 integrin binding sequence of the matrix protein cho... more cyclicCHAD is a peptide representing the α2β1 integrin binding sequence of the matrix protein chondroadherin (CHAD), which in our hands proved effective at counteracting bone loss in ovariectomised mice by inhibiting osteoclastogenesis. Given that bone metastases are characterised by exacerbated osteoclast activity as well, we tested this therapy in mice intracardiacally injected with the osteotropic human breast cancer cell line MDA-MB-231. Treatment with cyclicCHAD significantly decreased cachexia and incidence of bone metastases, and induced a trend of reduction of visceral metastasis volume, while in orthotopically injected mice cyclicCHAD reduced tumour volume. In vitro studies showed its ability to impair tumour cell motility and invasion, suggesting a direct effect not only on osteoclasts but also on the tumour cell phenotype. Interestingly, when administered together with a suboptimal, poorly effective, dose of doxorubicin (DXR), cyclicCHAD improved survival and reduced visceral metastases volume to a level similar to that of the optimal dose of DXR alone. Taken together, these preclinical data suggest that cyclicCHAD is a new inhibitor of bone metastases, with an appreciable direct effect also on tumour growth and a synergistic activity in combination with low dose chemotherapy, underscoring an important translational impact.
Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different rel... more Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.
Scandinavian Journal of Urology and Nephrology, 1983
Serum immunoreactive PTH (iPTH) was measured in 74 patients with urolithiasis and correlated to t... more Serum immunoreactive PTH (iPTH) was measured in 74 patients with urolithiasis and correlated to the corresponding serum calcium values. Serum iPTH was measured using a rooster antibovine iPTH antiserum which crossreacted with the human hormone within the 44-68 amino acid residue region. Sixty-six of these patients had normal serum iPTH and calcium concentrations. Their calcium values varied from 2.2 mmol/l to 2.6 mmol/l and their serum iPTH concentrations were less than 0.6 micrograms/l. The remaining 8 patients with urolithiasis were judged to have primary hyperparathyroidism because of an abnormal iPTH/calcium relationship. These patients had serum calcium concentrations varying from 2.6 mmol/l to 3.4 mmol/l and iPTH concentrations between 0.35 micrograms/l and 3.03 micrograms/l. The diagnosis was verified histologically in 7 patients after operation. In the last patient iPTH was reduced from 1.01 micrograms/l to 0.21 micrograms/l after surgery, and serum calcium changed from 2.6 mmol/l to 2.2 mmol/l. The combined evaluation of serum iPTH and calcium may improve the diagnosis for hyperparathyroidism and was in our series helpful in making a correct diagnosis in 2 out of 7 patients who had histologically verified disease. In addition, iPTH measurements are valuable to rule out hyperparathyroidism as the cause of hypercalcaemia.
Objectives: Caring for a dying family member is known to interfere with sleep, yet little is know... more Objectives: Caring for a dying family member is known to interfere with sleep, yet little is known about caregiver sleep once the patient is admitted to hospice. The aim of this pilot study was to describe the sleep of partners and other family caregivers of patients in hospice. Methods: The pilot study used a cross-sectional, descriptive, and comparative design. Participants included the primary family caregivers of patients recently admitted to a hospice in Norway. Caregiver sleep during the prior month was measured with the Pittsburgh Sleep Quality Index (PSQI). During the patient's hospice stay, caregiver sleep was measured using wrist actigraphy for four nights and three days. Results: Twenty family caregivers (12 partners and 8 other relatives) completed the study protocol without difficulty. On the PSQI, most caregivers (n = 13) reported clinically significant sleep problems during the prior month. Once the patient was admitted to hospice, actigraphy indicated that 10 caregivers had clinically significant sleep disruption (≥15% wake after sleep onset) and six averaged <7 hours of sleep per night. Partner caregivers reported more trouble falling asleep, and less sleep medication use, in the prior month than other types of family caregivers. However, once the patient was admitted to hospice, and after adjusting for caregiver age, partner caregivers experienced less sleep disruption than other caregivers. Significance of results: Findings demonstrate feasibility of the study protocol and indicate that sleep problems are common for caregivers of dying patients, even after the patient is admitted to hospice. The caregiver's relationship to the patient may be an important factor to consider in future studies.
Precursor B cell production from bone marrow in mice and humans declines with age. Because the me... more Precursor B cell production from bone marrow in mice and humans declines with age. Because the mechanisms behind are still unknown, we studied five precursor B cell subsets (ProB, PreBI, PreBII large, PreBII small, immature B) and their differentiation-stage characteristic gene expression profiles in healthy individual toddlers and middle-aged adults. Notably, the composition of the precursor B cell compartment did not change with age. The expression levels of several transcripts encoding V(D)J recombination factors were decreased in adults as compared with children: RAG1 expression was significantly reduced in ProB cells, and DNA-PKcs, Ku80, and XRCC4 were decreased in PreBI cells. In contrast, TdT was 3-fold upregulated in immature B cells of adults. Still, N-nucleotides, P-nucleotides, and deletions were similar for IGH and IGK junctions between children and adults. PreBII large cells in adults, but not in children, showed highly upregulated expression of the differentiation inhibitor, inhibitor of DNA binding 2 (ID2), in absence of changes in expression of the ID2-binding partner E2A. Further, we identified impaired Ig locus contraction in adult precursor B cells as a likely mechanism by which ID2-mediated blocking of E2A function results in reduced bone marrow B cell output in adults. The reduced B cell production was not compensated by increased proliferation in adult immature B cells, despite increased Ki67 expression. These findings demonstrate distinct regulatory mechanisms in B cell differentiation between adults and children with a central role for transcriptional regulation of ID2.
Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affecte... more Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affected by environmental factors, but has a strong heritable component. Despite recent large genome-wide association studies, few genetic risk factors for blood pressure have been identified. Epidemiological studies suggest associations between blood pressure and several diseases and traits, which may partly arise from a shared genetic basis (genetic pleiotropy). Using genome-wide association studies summary statistics and a genetic pleiotropy-informed conditional false discovery rate method, we systematically investigated genetic overlap between systolic blood pressure (SBP) and 12 comorbid traits and diseases. We found significant enrichment of single nucleotide polymorphisms associated with SBP as a function of their association with body mass index, low-density lipoprotein, waist/hip ratio, schizophrenia, bone mineral density, type 1 diabetes mellitus, and celiac disease. In contrast, the magnitude of enrichment due to shared polygenic effects was smaller with the other phenotypes (triglycerides, high-density lipoproteins, type 2 diabetes mellitus, rheumatoid arthritis, and height). Applying the conditional false discovery rate method to the enriched phenotypes, we identified 62 loci associated with SBP (false discovery rate <0.01), including 42 novel loci. The observed polygenic overlap between SBP and several related disorders indicates that the epidemiological associations are not mediated solely via lifestyle factors but also reflect an etiologic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to lipid biology and the immune system in SBP.
In GH4C1 cells, the calmodulin antagonist trifluoperazine (TFP) showed a dose-dependent, biphasic... more In GH4C1 cells, the calmodulin antagonist trifluoperazine (TFP) showed a dose-dependent, biphasic effect on the basal release of PRL. An inhibition of PRL release was observed with 15-50 mumol/l TFP, whereas a concentration of 100 mumol/l and above had a stimulatory effect. The increase in basal hormone release evoked by TRH (1 mumol/l) and high extracellular concentration of K+ (50 mmol/l) was eliminated by 30 mumol/l TFP. The stimulatory effect of 100 mumol/l TFP on basal hormone release was not affected by addition of TRH (1 mumol/l) or K+ (50 mmol/l). The Ca2+ antagonists Co2+ (5 mmol/l) and verapamil (100 mumol/l), and the Ca2+ chelator EgTA (4 mmol/l) abolished the stimulatory effect of TRH (1 mumol/l) and of K+ (50 mmol/l) on PRL release, whereas only Co2+ inhibited the stimulation caused by 100 mumol/l TFP. TFP (75 mumol/l) caused a transient increase in the concentration of cellular cAMP. Incubation of intact GH4C1 cells with TFP (75 mumol/l), had an inhibitory effect on both the low and the high affinity form of cAMP phosphodiesterase. Basal as well as TRH-stimulated adenyl cyclase activity were inhibited by TFP, and this effect was counteracted by addition of calmodulin.
The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical mem... more The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical membrane properties and transmembrane Ca2+ fluxes have been studied in a clonal strain of rat pituitary adenoma cells (GH3). These cells generate Ca2+ dependent action potentials, and produce and secrete spontaneously both Prl and growth hormone. Prl release stimulated by thyroliberin (TRH) and elevated extracellular K+ concentration was completely blocked by bromocriptine, whereas the basal release was only moderately affected. The TRH and K+ evoked Prl release were half maximally inhibited by bromocriptine at 5-10 and 10-50 microM, respectively. The normal biphasic membrane response to TRH and the depolarizing effect of elevated K+ concentration were not altered by bromocriptine, whereas the Ca2+- spikes in Na+-free solution were suppressed by the drug. We therefore suggest that bromocriptine blocks the voltage sensitive Ca2+-channels of GH3 cell. In agreement with this notion, bromocriptine also suppressed the basal and TRH induced 45Ca2+ efflux from preloaded cells. We conclude that the inhibitory effect of bromocriptine on the voltage dependent Ca2+- channels is an important mechanism responsible for suppression of Prl release.
We have studied the relationship between the prolaction (PRL) release induced by thyroliberin (TR... more We have studied the relationship between the prolaction (PRL) release induced by thyroliberin (TRH) and theophylline and the formation and inactivation of adenosine 3', 5'-cyclic monophosphate (cyclic AMP) in cultured rat-pituitary cells (GH3 cells). TRH, which stimulated prolactin release, increased cyclic AMP formation and stimulated transiently both the low- and high-Km cyclic phosphodiesterases. The maximal effect on the phosphodiesterase was observed at 30 mM TRH. The stimulatory effect of TRH on the activity of the cyclic AMP phosphodiesterases was duplicated by incubation of the cells with cyclic AMP (2-10 mM). In washed particulate GH3 cell fractions, TRH increased the adenylyl cyclase activity up to 180%. Treatment of GH3 cells with theophylline stimulated the release of PRL and inhibited cyclic AMP degradation probably leading to the measured increase in cellular concentrations of the nucleotide. The effects of TRH and theophylline on cellular cyclic AMP concentrat...
cyclicCHAD is a peptide representing the α2β1 integrin binding sequence of the matrix protein cho... more cyclicCHAD is a peptide representing the α2β1 integrin binding sequence of the matrix protein chondroadherin (CHAD), which in our hands proved effective at counteracting bone loss in ovariectomised mice by inhibiting osteoclastogenesis. Given that bone metastases are characterised by exacerbated osteoclast activity as well, we tested this therapy in mice intracardiacally injected with the osteotropic human breast cancer cell line MDA-MB-231. Treatment with cyclicCHAD significantly decreased cachexia and incidence of bone metastases, and induced a trend of reduction of visceral metastasis volume, while in orthotopically injected mice cyclicCHAD reduced tumour volume. In vitro studies showed its ability to impair tumour cell motility and invasion, suggesting a direct effect not only on osteoclasts but also on the tumour cell phenotype. Interestingly, when administered together with a suboptimal, poorly effective, dose of doxorubicin (DXR), cyclicCHAD improved survival and reduced visceral metastases volume to a level similar to that of the optimal dose of DXR alone. Taken together, these preclinical data suggest that cyclicCHAD is a new inhibitor of bone metastases, with an appreciable direct effect also on tumour growth and a synergistic activity in combination with low dose chemotherapy, underscoring an important translational impact.
Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different rel... more Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.
Scandinavian Journal of Urology and Nephrology, 1983
Serum immunoreactive PTH (iPTH) was measured in 74 patients with urolithiasis and correlated to t... more Serum immunoreactive PTH (iPTH) was measured in 74 patients with urolithiasis and correlated to the corresponding serum calcium values. Serum iPTH was measured using a rooster antibovine iPTH antiserum which crossreacted with the human hormone within the 44-68 amino acid residue region. Sixty-six of these patients had normal serum iPTH and calcium concentrations. Their calcium values varied from 2.2 mmol/l to 2.6 mmol/l and their serum iPTH concentrations were less than 0.6 micrograms/l. The remaining 8 patients with urolithiasis were judged to have primary hyperparathyroidism because of an abnormal iPTH/calcium relationship. These patients had serum calcium concentrations varying from 2.6 mmol/l to 3.4 mmol/l and iPTH concentrations between 0.35 micrograms/l and 3.03 micrograms/l. The diagnosis was verified histologically in 7 patients after operation. In the last patient iPTH was reduced from 1.01 micrograms/l to 0.21 micrograms/l after surgery, and serum calcium changed from 2.6 mmol/l to 2.2 mmol/l. The combined evaluation of serum iPTH and calcium may improve the diagnosis for hyperparathyroidism and was in our series helpful in making a correct diagnosis in 2 out of 7 patients who had histologically verified disease. In addition, iPTH measurements are valuable to rule out hyperparathyroidism as the cause of hypercalcaemia.
Objectives: Caring for a dying family member is known to interfere with sleep, yet little is know... more Objectives: Caring for a dying family member is known to interfere with sleep, yet little is known about caregiver sleep once the patient is admitted to hospice. The aim of this pilot study was to describe the sleep of partners and other family caregivers of patients in hospice. Methods: The pilot study used a cross-sectional, descriptive, and comparative design. Participants included the primary family caregivers of patients recently admitted to a hospice in Norway. Caregiver sleep during the prior month was measured with the Pittsburgh Sleep Quality Index (PSQI). During the patient's hospice stay, caregiver sleep was measured using wrist actigraphy for four nights and three days. Results: Twenty family caregivers (12 partners and 8 other relatives) completed the study protocol without difficulty. On the PSQI, most caregivers (n = 13) reported clinically significant sleep problems during the prior month. Once the patient was admitted to hospice, actigraphy indicated that 10 caregivers had clinically significant sleep disruption (≥15% wake after sleep onset) and six averaged <7 hours of sleep per night. Partner caregivers reported more trouble falling asleep, and less sleep medication use, in the prior month than other types of family caregivers. However, once the patient was admitted to hospice, and after adjusting for caregiver age, partner caregivers experienced less sleep disruption than other caregivers. Significance of results: Findings demonstrate feasibility of the study protocol and indicate that sleep problems are common for caregivers of dying patients, even after the patient is admitted to hospice. The caregiver's relationship to the patient may be an important factor to consider in future studies.
Precursor B cell production from bone marrow in mice and humans declines with age. Because the me... more Precursor B cell production from bone marrow in mice and humans declines with age. Because the mechanisms behind are still unknown, we studied five precursor B cell subsets (ProB, PreBI, PreBII large, PreBII small, immature B) and their differentiation-stage characteristic gene expression profiles in healthy individual toddlers and middle-aged adults. Notably, the composition of the precursor B cell compartment did not change with age. The expression levels of several transcripts encoding V(D)J recombination factors were decreased in adults as compared with children: RAG1 expression was significantly reduced in ProB cells, and DNA-PKcs, Ku80, and XRCC4 were decreased in PreBI cells. In contrast, TdT was 3-fold upregulated in immature B cells of adults. Still, N-nucleotides, P-nucleotides, and deletions were similar for IGH and IGK junctions between children and adults. PreBII large cells in adults, but not in children, showed highly upregulated expression of the differentiation inhibitor, inhibitor of DNA binding 2 (ID2), in absence of changes in expression of the ID2-binding partner E2A. Further, we identified impaired Ig locus contraction in adult precursor B cells as a likely mechanism by which ID2-mediated blocking of E2A function results in reduced bone marrow B cell output in adults. The reduced B cell production was not compensated by increased proliferation in adult immature B cells, despite increased Ki67 expression. These findings demonstrate distinct regulatory mechanisms in B cell differentiation between adults and children with a central role for transcriptional regulation of ID2.
Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affecte... more Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affected by environmental factors, but has a strong heritable component. Despite recent large genome-wide association studies, few genetic risk factors for blood pressure have been identified. Epidemiological studies suggest associations between blood pressure and several diseases and traits, which may partly arise from a shared genetic basis (genetic pleiotropy). Using genome-wide association studies summary statistics and a genetic pleiotropy-informed conditional false discovery rate method, we systematically investigated genetic overlap between systolic blood pressure (SBP) and 12 comorbid traits and diseases. We found significant enrichment of single nucleotide polymorphisms associated with SBP as a function of their association with body mass index, low-density lipoprotein, waist/hip ratio, schizophrenia, bone mineral density, type 1 diabetes mellitus, and celiac disease. In contrast, the magnitude of enrichment due to shared polygenic effects was smaller with the other phenotypes (triglycerides, high-density lipoproteins, type 2 diabetes mellitus, rheumatoid arthritis, and height). Applying the conditional false discovery rate method to the enriched phenotypes, we identified 62 loci associated with SBP (false discovery rate <0.01), including 42 novel loci. The observed polygenic overlap between SBP and several related disorders indicates that the epidemiological associations are not mediated solely via lifestyle factors but also reflect an etiologic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to lipid biology and the immune system in SBP.
In GH4C1 cells, the calmodulin antagonist trifluoperazine (TFP) showed a dose-dependent, biphasic... more In GH4C1 cells, the calmodulin antagonist trifluoperazine (TFP) showed a dose-dependent, biphasic effect on the basal release of PRL. An inhibition of PRL release was observed with 15-50 mumol/l TFP, whereas a concentration of 100 mumol/l and above had a stimulatory effect. The increase in basal hormone release evoked by TRH (1 mumol/l) and high extracellular concentration of K+ (50 mmol/l) was eliminated by 30 mumol/l TFP. The stimulatory effect of 100 mumol/l TFP on basal hormone release was not affected by addition of TRH (1 mumol/l) or K+ (50 mmol/l). The Ca2+ antagonists Co2+ (5 mmol/l) and verapamil (100 mumol/l), and the Ca2+ chelator EgTA (4 mmol/l) abolished the stimulatory effect of TRH (1 mumol/l) and of K+ (50 mmol/l) on PRL release, whereas only Co2+ inhibited the stimulation caused by 100 mumol/l TFP. TFP (75 mumol/l) caused a transient increase in the concentration of cellular cAMP. Incubation of intact GH4C1 cells with TFP (75 mumol/l), had an inhibitory effect on both the low and the high affinity form of cAMP phosphodiesterase. Basal as well as TRH-stimulated adenyl cyclase activity were inhibited by TFP, and this effect was counteracted by addition of calmodulin.
The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical mem... more The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical membrane properties and transmembrane Ca2+ fluxes have been studied in a clonal strain of rat pituitary adenoma cells (GH3). These cells generate Ca2+ dependent action potentials, and produce and secrete spontaneously both Prl and growth hormone. Prl release stimulated by thyroliberin (TRH) and elevated extracellular K+ concentration was completely blocked by bromocriptine, whereas the basal release was only moderately affected. The TRH and K+ evoked Prl release were half maximally inhibited by bromocriptine at 5-10 and 10-50 microM, respectively. The normal biphasic membrane response to TRH and the depolarizing effect of elevated K+ concentration were not altered by bromocriptine, whereas the Ca2+- spikes in Na+-free solution were suppressed by the drug. We therefore suggest that bromocriptine blocks the voltage sensitive Ca2+-channels of GH3 cell. In agreement with this notion, bromocriptine also suppressed the basal and TRH induced 45Ca2+ efflux from preloaded cells. We conclude that the inhibitory effect of bromocriptine on the voltage dependent Ca2+- channels is an important mechanism responsible for suppression of Prl release.
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Papers by Kaare Gautvik