J. Vasc. Biol. 42, Sup:2 (2005) pp114-115

P328 The effects of ghrelin on adenylyl cyclase and phosphalipase C activity in rat aorta.
1F.Ademoglu, 1N.Abacýoglu, 2E.Baloglu, 2H.Gurdal
1Department of Pharmacology, Gazi University, Faculty of Pharmacy, Ankara, TR; 2Department of Pharmacology and Clinical Pharmacology, Ankara University School of Medicine, Ankara, TR.

Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is a recently isolated hormone. Ghrelin and its receptor show a widespread distribution in the body including the blood vessels and the heart. In some studies, it has been shown that ghrelin could produce vasorelaxation response in human vessels. It stimulates different signal transduction mechanisms on different tissues and there are contradictory results about its effect on the vascular system. The identification of the ghrelin mediated signaling pathway will clarify the underlying mechanisms of its vascular effect. To ascertain the intracellular mechanisms mediating the action of ghrelin in rat aorta, we evaluated the effect of ghrelin on adenylyl cyclase and phosphalipase C activity. Ghrelin was able to significantly stimulate cAMP production in levels comparable to isoproterenol stimulation. While isoproterenol produced vasorelaxation on phenylephrine-induced contractions in rat aorta with intact or removed endothelium, ghrelin did not have any effect on this response. Furthermore, ghrelin also stimulated IP accumulation at a level comparable to noradrenalin induced response in rat aorta. However, it did not produce vasocontraction response in rat aorta as noradrenalin did. Based on these findings, it can be proposed that no effect of ghrelin on agonist stimulated contraction or basal tonus of rat aorta can be a result of concomitant activation of two contradictory signaling pathways, cAMP response for vasorelaxation and IP accumulation for vasocontraction.

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