Ouabain distinguishes between nicotinic and muscarinic receptor-mediated catecholamine secretions in perfused adrenal glands of cat.
1. The effect of ouabain on catecholamine (adrenaline and noradrenaline) secretion induced by agents acting on cholinoceptors was studied in perfused cat adrenal glands. Acetylcholine (ACh) (5 x 10(-7) to 10(-3) M), pilocarpine (10(-5) to 10(-3) M) and nicotine (10(-6) to 5 x 10(-5) M) caused dose-dependent increases in catecholamine secretion. Both ACh and nicotine released more noradrenaline than adrenaline and the reverse was the case for pilocarpine. 2. Ouabain (10(-5) M) enhanced catecholamine secretion induced by ACh (10(-5) M), pilocarpine (10(-3) M) and nicotine (3 x 10(-6) M) during perfusion with Locke solution. The ratio of adrenaline to noradrenaline was not affected by ouabain. 3. In the absence of extracellular Ca2+, ACh and pilocarpine, but not nicotine, still caused a small increase in catecholamine secretions, which were enhanced by treatment with ouabain (10(-5) M) plus Ca2+ (2.2 mM) for 25 min. The effect of ouabain was much more significant on noradrenaline secretion than on adrenaline secretion. The enhanced response was blocked by atropine (10(-6) M) but not by hexamethonium (5 x 10(-4) M). 4. Nifedipine (2 x 10(-6) M) inhibited the responses to pilocarpine and nicotine. The treatment with ouabain (10(-5) M) reversed only the response to pilocarpine and resulted in a significant increase in the proportion of noradrenaline released. 5. It is suggested that ouabain enhances evoked catecholamine secretions by facilitating Ca2+ entry through nicotinic receptor-linked Ca2+ channels and by increasing the intracellular Ca2+ pool linked to muscarinic receptors.
Yamada
Y
Y
Department of Pharmacology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Nakazato
Y
Y
Ohga
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D004837:Epinephrine / Q000378:metabolism*; D005260:Female; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D010862:Pilocarpine; D010042:Ouabain; D009538:Nicotine; D000109:Acetylcholine; D009638:Norepinephrine; D004837:Epinephrine