Voltage-independent catecholamine release mediated by the activation of muscarinic receptors in guinea-pig adrenal glands.
1. The differences between the mechanisms of muscarinic and nicotinic receptor-mediated catecholamine secretion with respect to their dependence on voltage changes and extracellular Ca were examined using perfused adrenal glands of the guinea-pig. 2. Acetylcholine (ACh, 10(-6) to 10(-3) M) caused a dose-dependent increase in catecholamine secretion. The ED50 value for ACh was 7 x 10(-5) M. In the presence of atropine (10(-5) M), the dose-response curve for ACh was shifted to the right. Hexamethonium (5 x 10(-4) M) preferentially reduced the responses to higher concentrations of ACh (greater than 10(-5) M). Pilocarpine (5 x 10(-4) M) and nicotine (3 x 10(-5) M) also stimulated catecholamine release. 3. During perfusion with isotonic KCl solution, ACh and pilocarpine, but not nicotine, evoked catecholamine secretion. These responses were abolished by atropine (10(-6) M). Pilocarpine-stimulated catecholamine secretion was enhanced during perfusion with isotonic KCl solution. Under these conditions, hexamethonium (10(-3) M) significantly augmented ACh-evoked catecholamine release. 4. During perfusion with either Ca-free isotonic KCl or Ca-free Locke solution, ACh and pilocarpine caused a partial increase in catecholamine secretion whereas nicotine and high K solution (56 mM) did not. The responses to ACh and pilocarpine were completely inhibited by atropine but not by hexamethonium. 5. When guinea-pig adrenal glands were perfused with isotonic KCl solution containing 2.2 mM Ca which was subsequently removed and replaced with EGTA, ACh-induced catecholamine secretion was similar in magnitude to that observed during perfusion with Locke solution. 6. We conclude that both nicotinic and muscarinic receptors are involved in ACh-induced catecholamine secretion from guinea-pig adrenal chromaffin cells. Activation of muscarinic or nicotinic receptors appears to stimulate catecholamine release through different mechanisms with respect to both voltage-dependence and Ca requirements.
Nakazato
Y
Y
Department of Pharmacology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ohga
A
A
Oleshansky
M
M
Tomita
U
U
Yamada
Y
Y
D000109:Acetylcholine / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D002395:Catecholamines; D006584:Hexamethonium Compounds; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D009538:Nicotine; D001285:Atropine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium