The specificity of ketanserin in the inhibition of serotonin-induced steroidogenesis in the rat adrenal zona glomerulosa.
Although the biological effects of ketanserin were originally attributed to its specific interaction with serotonin type 2 (5HT2) receptors, at high doses (greater than 10(-8)M) it also appears to act as an alpha 1-antagonist in some tissues. This in vitro study examines the possibility that Ketanserin may inhibit serotonin-induced steroidogenesis by blockade of alpha 1-receptors. Rat zona glomerulosa cells prepared by collagenase digestion of adrenal capsular tissue were incubated at 37 degrees C in Krebs-Ringer bicarbonate buffer (0.2% glucose, 0.2% bovine serum albumin) for 30 min with increasing doses of serotonin (10(-9)-10(-6)M) alone or in the presence of ketanserin (10(-6)M), methysergide (a 5HT-receptor antagonist) 10(-6)M) or prazosin (an alpha 1-antagonist)(10(-6)M). Cyclic AMP, Corticosterone and aldosterone outputs were measured by radioimmunoassay. Serotonin produced correlative sigmoidal dose responses for cyclic AMP, corticosterone and aldosterone which were inhibited by ketanserin and methysergide but not by prazosin. These results suggest that ketanserin does not act by alpha 1-blockade in the adrenal zona glomerulosa but rather as a specific 5HT-receptor antagonist.
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin; D008784:Methysergide / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000450:Aldosterone; D007650:Ketanserin; D000242:Cyclic AMP; D003345:Corticosterone; D011224:Prazosin; D008784:Methysergide