Muscarinic receptor subtypes mediating catecholamine secretion and increase in intracellular Ca2+ concentration in adrenal chromaffin cells of the guinea pig.
Muscarinic receptor subtypes mediating catecholamine secretion and increase in the intracellular concentration of Ca2+ ([Ca2+]i) were examined using muscarinic agonists and antagonists in dispersed adrenal chromaffin cells of the guinea pig. All muscarinic agonists (1-1,000 microM) tested caused increases in adrenaline secretion in a dose-dependent manner. Muscarine and methacholine were more effective than bethanechol, oxotremorine and pilocarpine. Muscarine and oxotremorine caused a small increase in adrenaline secretion even in the absence of extracellular Ca2+. Both 4-DAMP (0.1 microM) and pirenzepine (0.1 microM), but not methoctramine (0.1 microM), shifted the dose-response curve for muscarine-induced adrenaline secretion to the right. These muscarinic agonists also caused increase in [Ca2+]i in the presence of extracellular Ca2+. Muscarine-induced [Ca2+]i rises were reduced, but not abolished, by removal of extracellular Ca2+. These results suggest that catecholamine secretion induced by muscarinic agonists is mediated through M1, or M1 and M3 muscarinic receptor subtypes in adrenal chromaffin cells of the guinea pig.
Asano
T
T
Laboratory of Pharmacology, Hokkaido University, Sapporo, Japan.
Ohta
T
T
Otsuguro
K
K
Ito
S
S
Nakazato
Y
Y
D000313:Adrenal Medulla / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018678:Cholinergic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009116:Muscarine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*
D018678:Cholinergic Agents; D003959:Diamines; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010890:Pirenzepine; D010095:Oxotremorine; D009116:Muscarine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C054938:methoctramine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine