Effects of brain serotonin alterations on prostaglandin E1-induced bradycardia in rats.
The vasodepressor and bradycardia responses of saline control, serotonin-depleted and serotonin-potentiated rats to an intravenous dose of prostaglandin E1 (PGE1) were assessed under the urethane anesthesia. Elevation of serotonin concentration in brain with either 5-hydroxytryptophan (a serotonin precursor) or chlorimipramine (an inhibitor of serotonin reuptake), although causing no changes in vasodepressor reuptake), although causing no changes in vasodepressor response, did enhance the PGE1-induced bradycardia in contrast, depleting serotonin concentration in brain with either p-chlorophenylalanine or 5,7-dihydroxytryptamine greatly reduced the PGE1-induced bradycardia without changes in vasodepressor response. Moreover, the reduced PGE1 bradycardia induced by p-chlorophenylalanine treatment was readily reversed by the replacement of the depleted brain serotonin with 5-hydroxytryptophan in combination with a peripheral decarboxylase inhibitor Ro4-4602. The data indicate that brain serotonergic systems play a role in the elaboration or modulation of the PGE1-induced bradycardia. Specifically, brain serotonin seems to facilitate the PGE1-induced bradycardia since its depletion causes a decrease and its potentiation or elevation causes an increase in the PGE1-induced bradycardia.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D011458:Prostaglandins E; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D001545:Benserazide; D006916:5-Hydroxytryptophan; D010134:Fenclonine