(5E)- and (5Z)-carbacyclin are prostacyclin (PGI2) analogues endowed with antiaggregating and vasodilator properties, which stimulate adenylate cyclase activity in membranes from human platelets and cultured myocytes from rabbit mesenteric artery. In platelets they display the same efficacy as prostaglandin E1 (PGE1), and hence PGI2 both as activators of adenylate cyclase and as inhibitors of aggregation. In contrast, in vascular smooth muscle cells (5Z)-carbacyclin fails to produce the same degree of stimulation of the enzyme as PGI2, (5E)-carbacyclin and PGE1, nor does it induce the maximal relaxation of the mesenteric artery as do the other prostaglandins. (5Z)-carbacyclin is also able to antagonize the activation of adenylate cyclase and the relaxation elicited by PGE1 or PGI2 in the mesenteric artery, and therefore it displays partial agonist properties in these cells. We conclude that the receptors for PGI2 coupled to adenylate cyclase in platelets and vascular smooth muscle cells are different from each other, because (5Z)-carbacyclin can discriminate between them, being a partial agonist at myocyte but not at platelet level.

(5Z)-carbacyclin discriminates between prostacyclin-receptors coupled to adenylate cyclase in vascular smooth muscle and platelets / A. Corsini, G.C. Folco, R. Fumagalli, S. Nicosia, M.A. Noe, D. Oliva. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 90:1(1987), pp. 255-261. [10.1111/j.1476-5381.1987.tb16847.x]

(5Z)-carbacyclin discriminates between prostacyclin-receptors coupled to adenylate cyclase in vascular smooth muscle and platelets

A. Corsini
Primo
;
G.C. Folco;S. Nicosia;
1987

Abstract

(5E)- and (5Z)-carbacyclin are prostacyclin (PGI2) analogues endowed with antiaggregating and vasodilator properties, which stimulate adenylate cyclase activity in membranes from human platelets and cultured myocytes from rabbit mesenteric artery. In platelets they display the same efficacy as prostaglandin E1 (PGE1), and hence PGI2 both as activators of adenylate cyclase and as inhibitors of aggregation. In contrast, in vascular smooth muscle cells (5Z)-carbacyclin fails to produce the same degree of stimulation of the enzyme as PGI2, (5E)-carbacyclin and PGE1, nor does it induce the maximal relaxation of the mesenteric artery as do the other prostaglandins. (5Z)-carbacyclin is also able to antagonize the activation of adenylate cyclase and the relaxation elicited by PGE1 or PGI2 in the mesenteric artery, and therefore it displays partial agonist properties in these cells. We conclude that the receptors for PGI2 coupled to adenylate cyclase in platelets and vascular smooth muscle cells are different from each other, because (5Z)-carbacyclin can discriminate between them, being a partial agonist at myocyte but not at platelet level.
Alprostadil; Animals; Stereoisomerism; Mesenteric Arteries; Humans; Adenylate Cyclase; Rabbits; Receptors, Epoprostenol; Blood Platelets; Platelet Aggregation; Cells, Cultured; Muscle, Smooth, Vascular; Receptors, Prostaglandin; Epoprostenol; Muscle Relaxation; Male
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/184438
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