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Honey was used to treat wounds since ancient times till nowadays. The present study aimed at preparing a honey-based hydrogel and assay its antimicrobial properties and wound healing activity; in-vitro and in-vivo. Topical honey hydrogel... more
Honey was used to treat wounds since ancient times till nowadays. The present study aimed at preparing a honey-based hydrogel and assay its antimicrobial properties and wound healing activity; in-vitro and in-vivo. Topical honey hydrogel formulations were prepared using three honey concentrations with gelling agents; chitosan and carbopol 934. The prepared formulae were evaluated for pH, spreadability, swelling index, in-vitro release and antimicrobial activity. The pH and spreadability were in the range of 4.3-6.8 and 5.7-8.6 cm, respectively. Chitosan-based hydrogel showed higher in-vitro honey release with diffusional exponent 'n ≤ 0.5 indicates Fickian diffusion mechanism. Hydrogel formulae were assessed for in-vitro antimicrobial activity using Disc Diffusion antibiotic sensitivity test against common burn infections bacteria; Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Streptococcus pyogenes. The 75% honey-chitosan hydrogel showed highest antimi...
Research Interests: Wound Healing and In Vivo
1 In Charles River CD 1 mice, a single dose of 100 mg kg-1 caffeine injected intraperitoneally on day 14 of pregnancy caused a low incidence of cleft palate in the fetuses. 2 Single oral doses of caffeine of 200 and 300 mg kg-1 but not... more
1 In Charles River CD 1 mice, a single dose of 100 mg kg-1 caffeine injected intraperitoneally on day 14 of pregnancy caused a low incidence of cleft palate in the fetuses. 2 Single oral doses of caffeine of 200 and 300 mg kg-1 but not 100 mg kg-1 on day 14, caused cleft palate in some of the fetuses, but was clearly toxic to the dams. 3 Oral doses of caffeine up to 300 mg kg-1 on day 14 of pregnancy did not reduce utero-placental blood flow, placental transfer function, or amniotic fluid volume. 4 An oral dose of 100 mg kg-1 caffeine induced a marked stimulation of adrenocortical secretion producing plasma corticosterone levels of 1248 ± 129 ?g per 100 ml by 2 h and with elevated levels persisting more than 8 h. 5 It is suggested that the elevated plasma corticosterone is the cause of the cleft palate induced in mice by caffeine. Since corticosterone is a known cleft palate inducer in mice but not in man these results do not predict a hazard from normal caffeine consumption in man.
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Development of enhanced UPLC-UV method for determination of nicotine in human plasma was achieved on a Symmetry(®) C18 column (100 mm × 2.1 mm, 2.2 μm) applying isocratic elution based on Methanol: Acetonitrile: Phosphate Buffer (pH: 2.7)... more
Development of enhanced UPLC-UV method for determination of nicotine in human plasma was achieved on a Symmetry(®) C18 column (100 mm × 2.1 mm, 2.2 μm) applying isocratic elution based on Methanol: Acetonitrile: Phosphate Buffer (pH: 2.7) with the ratio (20:30:50, v/v/v) as a mobile phase. The ultraviolet detector was operated at 260 nm. The mobile phase was pumped through the column at a flow rate of 0.2 mL min(-1). The column temperature was adjusted to 50ºC and the injection volume was 2 μL. Quinine was selected as an internal standard (IS) due to its structure similarity to nicotine having basic pyridine ring to optimize the liquid liquid extraction procedure using diethyl ether coupled with vacuum evaporation at 40°C. Validation parameters for nicotine were found to be acceptable over the concentration range of 2.5-50 ng ml(-1). The application of the proposed method on four healthy human volunteers was approved by the ethical committee. The study was carried out under fasting ...
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Research Interests: Chemistry, Biology, Adenosine, Brain, Blood Pressure, and 15 moreAnimals, Antimicrobial activity, CHEMICAL SCIENCES, Cisplatin, Antibacterial activity, Chickens, Bothrops, Coordination Polymer, Chromones, Bacillus Anthracis, Cell Survival, Antiemetics, Biochemistry and cell biology, CHO cells, and Antihypertensive agents
Corticosteroids are frequently used for their powerful anti-inflammatory activity in the management of various chronic inflammatory diseases. They are also used because of their potent immunosuppressive power in the manipulation of... more
Corticosteroids are frequently used for their powerful anti-inflammatory activity in the management of various chronic inflammatory diseases. They are also used because of their potent immunosuppressive power in the manipulation of adverse effects associated with chemotherapeutic treatments. However, their long-term usage is associated with several side effects. The majority of these side effects are due to the increased oxidative stress associated with their administration. Dexamethasone (DEX) is one of the most commonly used glucocorticoids either as an anti-inflammatory and/or immunosuppressive agent.Wogonin, a mono-flavonoid present in the root of Scutellaria baicalensis Georgi, has attracted considerable attention in recent years. Wogonin has a well-documented antioxidant activity that is mainly responsible for its multiple pharmacological activities. The current study aimed at investigating the possible protective activity of wogonin against DEX-induced oxidative stress in Spr...
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One of the most serious consequences of Schistosoma ( S. ) mansoni infection is hepatic schistosomiasis or periportal fibrosis. Treatment with praziquantel (PZQ) remains the mainstay of schistosomiasis control. Stem cells and their... more
One of the most serious consequences of Schistosoma ( S. ) mansoni infection is hepatic schistosomiasis or periportal fibrosis. Treatment with praziquantel (PZQ) remains the mainstay of schistosomiasis control. Stem cells and their possible use in cell therapy have drawn much attention recently, due to their potential for self - renewal and differentiation. The present study aimed to investigate the ability of mesenchymal stem cells (MSCs) to integrate into the livers of S. mansoni - infected mice. S. mansoni - infected mice (60±10 cercariae/mouse, s.c.) received intra hepatic i njection of MSCs (1.5x10 6 cells/mouse), alone or combined with oral PZQ (500 mg/kg/day, for 2 days, seven weeks post infection). At the 10 th month post infection, flow cytometry and immunohistochemical analysis for human - specific β2 - globulin were performed . Immunohistochemical results showed positive hepatic expression for β2 - globulin. Interestingly, the integration of MSCs was found to be enhanced ...
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Released oxygen plays a critical role in reducing destructive tumor behavior.
Research Interests: Materials Science and RSC
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Pegylated-interferon α-2a and ribavirin (PIFN/RBV), the current standard treatment for hepatitis C virus (HCV) infection in Egypt, is frequently associated with hematological adverse effects, leading to high treatment discontinuation... more
Pegylated-interferon α-2a and ribavirin (PIFN/RBV), the current standard treatment for hepatitis C virus (HCV) infection in Egypt, is frequently associated with hematological adverse effects, leading to high treatment discontinuation rates. The objective of the present study is to explore the effectiveness of intervening with folic acid (F) and/or vitamin B complex (B) compared with placebo (C) in HCV-treatment Egyptian patients for the management of treatment-induced deterioration of health related quality of life (HRQOL) as well as hematological parameter. In a randomized controlled trial, one hundred and sixty subjects were randomly assigned to receive PIFN/RBV in addition to BF, B, F, or C. Blood samples were collected at different time points during 48 weeks and at 12 and 24 weeks post treatment for complete blood count and for HCV RNA real time PCR. Short form SF 36V2 questionnaire were used to assess HRQOL at various time during and post treatment. Egyptian HCV patients treat...
9-Cis-retinoic acid (9-cis-RA) has been proposed to be the endogenous ligand of retinoid X receptors. We examined the plasma pharmacokinetics of 9-cis-RA and its metabolites in nonpregnant female NMRI mice after oral dosing with 50 mg... more
9-Cis-retinoic acid (9-cis-RA) has been proposed to be the endogenous ligand of retinoid X receptors. We examined the plasma pharmacokinetics of 9-cis-RA and its metabolites in nonpregnant female NMRI mice after oral dosing with 50 mg 9-cis-RA/kg body weight. Furthermore, we studied the metabolism of 9-cis-RA and its transfer to the embryo following oral administration of the precursor 9-cis-retinaldehyde (9-cis-RAL; 100 mg/kg body weight) to pregnant mice and rats on gestational days 11 and 13, respectively. Following 9-cis-RA administration, plasma levels of 9-cis-RA reached their maximum within 40-60 min and then declined in a monoexponential manner with an apparent half-life of 64 +/- 32 min. A great variety of polar metabolites of 9-cis-RA was found; among them, the beta-glucuronides of 9-cis-RA (9-cis-RAG) and of 9-cis-4-oxo-RA (9-cis-4-oxo-RAG) could be identified. A further prominent polar metabolite of 9-cis-RA in mouse plasma was shown to be an additional RA isomer (distin...
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Retinoic acid, an oxidative metabolite of vitamin A, is involved in the control of many biological processes including embryonic development. Excess as well as deficiency of retinoids were found to be teratogenic. The effects of retinoids... more
Retinoic acid, an oxidative metabolite of vitamin A, is involved in the control of many biological processes including embryonic development. Excess as well as deficiency of retinoids were found to be teratogenic. The effects of retinoids in normal as well as abnormal development may be mediated by two members of retinoid receptors, the RAR's and RXR's, which exhibit a specific temporal and spatial expression during development. The significance of the retinoid receptors was investigated here by studying the teratogenic effects of retinoid ligands with relative selectivity for binding and transactivation of the retinoic acid receptors RAR alpha, RAR beta and RAR gamma. Pregnant NMRI mice were administered 5 or 15 mg/kg of CD 336 (Am 580) (alpha-ligand), CD 2019 (beta-ligand), CD 437 (gamma-ligand) or 37.5 mg/kg all-trans-retinoic acid in 25% Cremophor EL on day 8.25 or day 11 of gestation by gastric intubation. External, visceral and skeletal malformations were observed on day 18 of gestation. The order of teratogenic potency was: alpha-ligand > beta-ligand > gamma-ligand. In addition, these retinoids also produced a different spectrum of defects. The alpha-ligand induced the most varied defects including severe ear, mandible, and limb malformations. The beta-ligand induced defects of the urinary system and liver in greater frequency than expected from its relative potency. The gamma-ligand preferentially induced ossification deficiencies and defects of the sternebrae and vertebral body. Our results show that these three retinoids, which were previously demonstrated to exhibit retinoid-like activities in several systems, exert differing teratogenic activities, in regard to both potency and regioselectivity: we hypothesize that the relative selectivity for binding and transactivation of the three retinoic acid receptors could possibly be related to the differences of teratogenic effects observed in this study. The low potency of the gamma-ligand may lead the way to interesting new retinoids with improved therapeutic ratio.
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The effects of praziquantel (CAS 55268-74-1) on serum glucose and insulin levels in normoglycemic and hyperglycemic rats were studied. Also the combined effect of praziquantel and glibenclamide (CAS 10238-21-8) on oral glucose tolerance... more
The effects of praziquantel (CAS 55268-74-1) on serum glucose and insulin levels in normoglycemic and hyperglycemic rats were studied. Also the combined effect of praziquantel and glibenclamide (CAS 10238-21-8) on oral glucose tolerance in rats was investigated. Praziquantel, given orally in a dose of 250 mg/kg, significantly increased serum glucose level in hyperglycemic rats without changing serum insulin level. After oral glucose load, praziquantel produced a significant increase in serum glucose level and antagonized the hypoglycemic action of glibenclamide. These results indicate that praziquantel significantly increased serum glucose level in both hyperglycemic rats and after glucose load. Since insulin levels are not significantly altered by praziquantel, the hyperglycemic effect of this drug may be attributed to inhibition of peripheral glucose utilization. Care should be taken if praziquantel is prescribed to diabetic patients.
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Cisplatin is a major classical anticancer agent. However, cisplatin-induced nephrotoxicity remains a major doselimiting side effect. Several studies have highlighted the role of catalytic iron content in several diseases including... more
Cisplatin is a major classical anticancer agent. However, cisplatin-induced nephrotoxicity remains a major doselimiting side effect. Several studies have highlighted the role of catalytic iron content in several diseases including cisplatin nephrotoxicity opening the doors for adding iron chelators as an adjunct therapy to cisplatin therapy. Since deferoxamine is the major approved chelation therapy in iron overload disorders, the current study was directed to exploring the possible nephroprotective outcomes of deferoxamine in an acute animal model of cisplatin-induced renal injury. Male Sprague-Dawley rats were injected i.p. daily for 6 consecutive days with 3 different dose levels of deferoxamine as follows: 100, 200, and 300 mg/kg. On day 3, cisplatin was injected i.p. as a single dose of 7.5 mg/kg, and animals were sacrificed on day 7. Measurement of serum creatinine and blood urea nitrogen (BUN) showed that iron chelation by deferoxamine failed to improve kidney function as dem...
Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c &/or irregular blood glucose... more
Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c &/or irregular blood glucose levels. Diabetic patient’s mortality rates with COVID-19 are higher than cardiovascular or cancer patients. Recently Bacillus Calmette–Guérin (BCG) has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to Beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from TB and leprosy and has been repositioned for treatment of bladder cancer, diabetes & multiple sclerosis. Recently, the COVID-19 epidemiological study confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compa...
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The ongoing development of anti-diabetic drugs brings a revolution in the treatment of diabetes mellitus. Dipeptidyl Peptidase-4 (DPP-4) inhibitors are considered a new class of oral anti-diabetic agents used in treatment of type 2... more
The ongoing development of anti-diabetic drugs brings a revolution in the treatment of diabetes mellitus. Dipeptidyl Peptidase-4 (DPP-4) inhibitors are considered a new class of oral anti-diabetic agents used in treatment of type 2 diabetes mellitus. Therefore, the necessity to explore and compare the existing analytical method used for estimation of such drugs either single or in combination is crucial. This review offers an overview of different HPLC-UV and spectrophotometric methods used for determination of DPP-4 inhibitors namely; sitagliptin, vildagliptin, saxagliptin, linaglitpin and alogliptin in a tabulated comparative way. In addition, the present work included stability indicating assays of the drugs and determination of their process related impurities. Spectrophotometric assays showed more facilitated, simple and cost effective methods than the reported chromatographic techniques. Furthermore, the reviewed spectrophotometric methods showed the advantages of low cost sol...
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin,... more
Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work. LC-MS/MS determination of once-weekly anti-diabetic DPP-4 inhibitors; omarigliptin & trelagliptin in plasma and brain tissue was employed after 2 h of oral administration to rats. The brain/plasma concentration ratio was used to deduce the penetration power through the BBB. Results showed that only omarigliptin crossed the BBB due to its low molecular weight & lipophilic properties suggesting its repositioning as antiparkinsonian agent. The results of B...
Targeting solid tumors transdermally is an emerging approach that is currently under intense investigation. In this context, microemulsions are reported as one of the most favored carriers for successful transdermal drug delivery.... more
Targeting solid tumors transdermally is an emerging approach that is currently under intense investigation. In this context, microemulsions are reported as one of the most favored carriers for successful transdermal drug delivery. Thereby, these nano-carriers were utilized in this study for the delivery of a phytochemical, namely methyl dihydrojasmonate (MDHJ), which has previously demonstrated an anticancer effect. Accordingly, pseudoternary phase diagrams were constructed using several combinations of oils, surfactants and co-surfactants and following the water titration method. Two systems were selected and an experimental design (Simplex Lattice Mixture Design) was utilized to select formulations for further investigation through an ex vivo permeation study through mouse skin. Transdermal fluxes were determined reaching a value of 0.07μlcm(-2)h(-1). Cytotoxicity studies were carried out where the selected superlative formulation was further investigated on MCF-7 cell lines and s...
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The present study considered the pharmacokinetic evaluation of empagliflozin after administration to Egyptian volunteers, and the results were compared with other ethnic populations. The FDA recognizes that standard methods of defining... more
The present study considered the pharmacokinetic evaluation of empagliflozin after administration to Egyptian volunteers, and the results were compared with other ethnic populations. The FDA recognizes that standard methods of defining racial subgroups are necessary to compare results across pharmacokinetic studies and to assess potential subgroup differences. The design of the study was as an open labeled, randomized, one treatment, one period, single dose pharmacokinetic study. The main pharmacokinetic parameters estimated were Cmax, Tmax, t1/2, elimination rate constant, AUC0-t and AUC0-inf. The insignificant difference in pharmacokinetic parameters between Egyptians and white German subjects suggests that no dose adjustment should be considered with administration of 25 mg empagliflozin to Egyptian population. A new LC-MS/MS method was developed and validated, allowing sensitive estimation of empagliflozin (25-600 ng mL(-1)) in human plasma using dapagliflozin as an internal sta...
The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in... more
The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50-60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost. To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years. An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone. The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013-0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which yielded an incremental cost-effectiveness ratio of -US$4206 per QALY gained. Thus, the combined therapy was dominant. All costs were reported in US dollars (USD) for the financial year 2014. The results of this analysis indicate that from the perspective of the Egyptian health sector, the addition of aspirin to the typical warfarin therapy is more effective and less costly for patients with mechanical valve prostheses than treatment with warfarin alone. This combined strategy could be adopted to prevent the complications of mechanical valve prostheses. Our study adds to the body of evidence supporting the option of warfarin-plus-aspirin therapy for patients with mechanical valve prostheses.
Research Interests: Marketing, Egypt, Adolescent, Applied Economics, Humans, and 14 moreFemale, Male, Young Adult, Thromboembolism, Anticoagulants, Aspirin, Middle Aged, Quality adjusted life years, Adult, Warfarin, Public health systems and services research, Cost Benefit Analysis, Combination drug therapy, and Platelet Aggregation Inhibitors
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Research Interests: Engineering, Pharmacokinetics, Pregnancy, Humans, Mice, and 15 moreCalibration, Female, Animals, High Pressure Liquid Chromatography, CHEMICAL SCIENCES, Retinoic Acid, Reproducibility of Results, Correlation coefficient, Bovine Serum Albumin, Embryos, Antineoplastic Agents, Ligands, Retinoic Acid Receptor, Reference standards, and Autoanalysis
Certain series of 2-thiohydantoin derivatives, carrying various substituents at position 5 such as 5-bromo-2-thienylmethylene, 5-(2-carboxyphenylthio)-2-thienylmethylene and 2-methylene-4H-thieno[2,3-b][1]benzothiopyran-4-one, were... more
Certain series of 2-thiohydantoin derivatives, carrying various substituents at position 5 such as 5-bromo-2-thienylmethylene, 5-(2-carboxyphenylthio)-2-thienylmethylene and 2-methylene-4H-thieno[2,3-b][1]benzothiopyran-4-one, were evaluated for their antitumor activity. Compound 5-(5-bromo-2-thienylmethylene)-3-morpholinomethyl-2-(2,3,4,6 -tetra-O-acetyl -beta-D-glucopyranosylthio)hydantoin proved to possess a broad spectrum antitumor activity against a wide range of different human cell lines of nine tumor subpanels causing both cytostatic and cytotoxic effects, resulting in full panel median growth inhibition (GI50) and total growth inhibition (TGI), with a median lethal concentration (LC50) at 15.1, 41.7 and 83.2 microM, respectively. On the other hand, compound 5-(5-bromo-2-thienylmethylene)-2-thiohydantoin and compound 5-(5-bromo-2-thienylmethylene)-3-phenyl-2- (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-thio)hydantoin showed potential selectivity against leukemia cell lines. Further derivatization of these compounds, deduced from the obtained tentative structure-activity relationships, may lead to more potent agents.
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Research Interests: Mitosis, Pregnancy, Reproductive toxicology, Mice, Female, and 11 moreAnimals, Blastocyst, Embryo Transfer, Public health systems and services research, Oocytes, Embryos, Mitotic Index, Gonadotropins, Superovulation, Paediatrics and reproductive medicine, and Pharmacology and pharmaceutical sciences
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GP-2-128 is a novel catecholamine designed for transdermal iontophoretic delivery in patients with limited mobility to prevent deconditioning and muscular wasting. We characterized the interactions of this agent with alpha- and... more
GP-2-128 is a novel catecholamine designed for transdermal iontophoretic delivery in patients with limited mobility to prevent deconditioning and muscular wasting. We characterized the interactions of this agent with alpha- and beta-adrenoceptors in vitro. In electrically stimulated rat left atria, GP-2-128 produced a concentration-dependent increase in contractile force. pD2 values for GP-2-128, isoproterenol (ISO), and dobutamine (DOB) were 10.6 +/- 0.12, 8.55 +/- 0.02, and 7.0 +/- 0.20, respectively. Metoprolol caused a shift in the concentration-effect curves for the three agonists. In spontaneously beating rat right atria, pD2 values of GP-2-128, ISO, and DOB are 10.4 +/- 0.24, 8.82 +/- 0.18, and 6.92 +/- 0.18, respectively. The affinity constant (KA) of GP-2-128, ISO, and DOB for cardiac beta 1-adrenoceptors was determined by competition binding assays to be 8.09, 6.04 and 4.49, respectively. In guinea pig trachea precontracted with histamine, GP-2-128 and ISO produced a concentration-dependent relaxation. pD2 values were 10.0 +/- 0.1 and 8.2 +/- 0.1, respectively. DOB was more potent than GP-2-128 in contracting isolated rat aortic rings (alpha 1 effect) and in displacing [3H]rauwolscine (alpha 2 effect). We also studied the interactions of GP-2-128 and ISO with the atypical beta-adrenoceptors (beta 3) in guinea pig ilea and rat and hamster adipocytes. Both agents inhibited twitches produced by transmural nerve stimulation in the presence of 10(-5) M nadolol. The EC30 for GP-2-128 and ISO at this atypical receptor site were 4.25 x 10(-10) and 5.05 x 10(-8) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)