Serotonin receptor activation of phosphoinositide turnover in uterine, fundal, vascular, and tracheal smooth muscle.
Hydrolysis of phosphatidylinositol is becoming recognized as the second messenger system for a number of hormones and neurotransmitters, including serotonin. The present study was designed to explore the effects of serotonin to enhance phosphoinositide turnover in several smooth muscle preparations, in an effort (a) to determine which smooth muscle preparation might provide a useful system for further study of phosphoinositide turnover and (b) to examine the role of 5-HT2 receptors in such responses. Basal-[3H]inositol monophosphate ([3H]IP) formation was 10-fold higher in the uterus than in the rat jugular vein, aorta, stomach fundus, or guinea pig trachea. Serotonin produced significant elevations in [3H]IP in the rat aorta, uterus, and jugular vein. Maximal elevation in [3H]IP was greatest in the jugular vein (eightfold increase) with an ED50 for serotonin of 0.4 microM. Serotonin (10(-7)-10(-4) M), although a potent contractile agonist in both the guinea pig trachea and rat stomach fundus, did not increase [3H]IP levels in these tissues. The selective 5-HT2 receptor blocker LY53857 (10(-8) M) antagonized the increase in [3H]IP produced by serotonin in the jugular vein, aorta, and uterus. Pargyline (10(-5) M) added to the trachea and fundus did not unmask an effect of serotonin or enhance the response to serotonin in the rat aorta. Thus, the jugular vein was the tissue most sensitive to activation of [3H]IP by serotonin. Increases in [3H]IP produced by serotonin may be linked to activation of 5-HT2 receptors in the jugular vein, aorta, and uterus since the selective 5-HT2 antagonist LY53857 could block this biochemical effect.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D005748:Gastric Fundus / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013045:Species Specificity; D014132:Trachea / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D004873:Ergolines; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D010293:Pargyline; C032663:LY 53857