Effects of muscarinic pharmacophores on the cholinergic regulation of catecholamine secretion from perfused adrenal glands.
The effects of the muscarinic antagonists, atropine, aprophen, azaprophen and pirenzepine, on catecholamine secretion stimulated by acetylcholine (ACh) and nicotine were studied using perfused and isolated guinea-pig adrenal glands. Sequential 2-min infusions of ACh (10(-5)M) at 15-min intervals evoked repetitive catecholamine secretory responses for at least 1 hr. This dose of ACh produced a predominantly muscarinic receptor-mediated catecholamine secretory response, which was inhibited by all muscarinic antagonists used. The order of potency was atropine greater than azaprophen greater than pirenzepine greater than aprophen, with IC50 values of 1.0 x 10(-9), 3.8 x 10(-9), 7.0 x 10(-8) and 1.3 x 10(-6) M, respectively. In comparison, repeated 1-min infusions of nicotine (2 x 10(-5) M) at 15-min intervals evoked progressively smaller catecholamine secretory responses over the course of 1 hr. At higher doses, atropine, azaprophen and aprophen also inhibited the nicotine-induced catecholamine secretion. In contrast, pirenzepine had no effect on the nicotinic response. The IC50 values for atropine, azaprophen and aprophen were 2.7 x 10(-6), 1.5 x 10(-6), and 3.2 x 10(-6) M, respectively. Because the antinicotinic effect of atropine and azaprophen was achieved at concentrations 2 to 3 orders of magnitude higher than those needed for the antimuscarinic effect, it was most likely not pharmacologically significant, but rather due to nonspecific inhibition of the nicotinic receptor.
Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Y
Y
Nakazato
M A
MA
Oleshansky
P K
PK
Chiang
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010477:Perfusion; D010666:Phenylpropionates / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects; D014326:Tropanes / Q000494:pharmacology
D002395:Catecholamines; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010666:Phenylpropionates; D011976:Receptors, Muscarinic; D014326:Tropanes; C052339:azaprophen; D010890:Pirenzepine; D011189:Potassium Chloride; D009538:Nicotine; D001285:Atropine; C006615:aprofen