Inositol phosphate production in response to [Arg8]vasopressin, endothelin 1, and prostaglandin F2 alpha in rat aorta and mesenteric arteries.
Vascular tissues such as rat aorta and mesenteric arteries are extensively used experimentally for the study of cardiovascular diseases. To further our understanding of the signal transduction mechanisms involved in responses to several potent vasoconstrictors, such as [Arg8]vasopressin (AVP), endothelin 1 (ET-1), and prostaglandin F2 alpha (PGF2 alpha), we have investigated the time course for production of inositol monophosphate (InsP1), bisphosphate (InsP2), and trisphosphate (InsP3) in response to these agonists as well as their relative potency for phosphatidylinositol hydrolysis. Time-course studies of production of the different inositol phosphates in response to AVP and PGF2 alpha showed an early increase after 15-30 s of stimulation. Thereafter InsP3 declined towards baseline, with a secondary increase towards steady state after 5-10 min. Rapid turnover of InsP3 was reflected by accumulation of InsP1 and InsP2 in the presence of LiCl (20 mM) to inhibit monophosphatases. After 15-30 min of stimulation, there was accumulation of the Ins(1,3,4)P3 isomer. All three agonists induced greater accumulation of InsP2 in mesenteric arteries than in thoracic aorta, suggesting that turnover of Ins(1,4,5)P3 may be faster in the former than in the latter. The accumulation of total inositol phosphates induced by maximum concentrations of ET-1 was greater than in response to AVP or PGF2 alpha. Dose-response curves showed that the rank order of potency for stimulation of production of inositol phosphates was AVP > ET-1 > PGF2 alpha, similar to the sensitivity of blood vessels to these agents. Comparison of responses to ET-1 and ET-3 showed that the receptors stimulated by endothelins were of the isopeptide selective ETA subtype.(ABSTRACT TRUNCATED AT 250 WORDS)
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Clinical Research Institute of Montreal, Que., Canada.
Nguyen
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PV
Yang
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Schiffrin
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D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism
D016232:Endothelins; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D001127:Arginine Vasopressin; D015237:Dinoprost; D010738:Type C Phospholipases