Characterization of a dopaminergic receptor that modulates adrenomedullary catecholamine release.
Nicotine evokes the release of catecholamines from bovine adrenal glands perfused with oxygenated Krebs-bicarbonate solution. Two 2-min pulses of 5 microM nicotine, at 40-min intervals (S1 and S2), gave net catecholamine outputs of 45.2 +/- 3.6 and 29.1 +/- 3.5 micrograms/8 min, respectively. Apomorphine (1 or 10 microM) markedly inhibited catecholamine release during S2 to 9.1 +/- 2.2 and 0.5 micrograms/8 min, respectively. Haloperidol (0.5 microM) reversed the inhibitory effects of apomorphine. Haloperidol alone enhanced catecholamine release induced by nicotine to 67.9 +/- 7.9 micrograms/8 min. [3H]Spiperone binds to adrenomedullary membranes with a KD of 0.24 nM and a Bmax of 117 fmol/mg of protein. Whereas spiperone and haloperidol potently displaced such binding, 3,4-dihydroxyphenylethylamine (dopamine) and sulpiride were poorer displacers, and SCH23390, prazosin, phenoxybenzamine, propranolol, BAY-K-8644, and nitrendipine did not displace [3H]spiperone bound. These data strongly suggest that, as in the cat, the bovine adrenal medulla chromaffin cell contains a dopaminergic receptor that modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. Such a receptor seems to be of the D2 type and might be involved in a sympatho-adrenal cooperative mechanism contributing to the maintenance of cardiovascular homeostasis during stressful situations as well as to the pathogenesis of hypertension. If so, selective dopaminergic agonists might prove clinically useful in the treatment of hypertension.
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001667:Binding, Competitive; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000378:metabolism
D002395:Catecholamines; D011954:Receptors, Dopamine; D013134:Spiperone; D009538:Nicotine; D006220:Haloperidol; D001058:Apomorphine