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Cell Biology International (2002) 26, 963–969 (Printed in Great Britain)

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PHARMACOLOGICAL CHARACTERISTICS OF NOVEL PUTATIVE PURINOCEPTORS IN VASCULAR ENDOTHELIUM

Shu‑Hong Liu, Li‑Mei Shan and Hai Wang^f1

Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China

Abstract

Using an isolated rat aorta with intact endothelium, a functional bioassay system was created as follows: pre-contract the isolated rat aorta with intact endothelium in the presence of 0.62μmol/l of norepinephrine, and then add acetylcholine to obtain maximal endothelium-dependent relaxation. In the addition of low concentration of adenosine, a P1 agonist or ATP, a P2 agonist to this system, the rat aorta smooth muscle contraction was observed. This observation could not be explained in terms of the classic P1 and P2 receptor properties, suggesting that there may be a novel subtype of purinoceptors in the endothelium of the rat aorta. The P1 and P2 agonists-induced rat aorta smooth muscle contraction could be blocked by the pretreatments of the bioassay system with a G protein (Gi/o) inhibitor, PTX, and EDNO synthesis inhibitor, L-NAME and cyclooxygenase inhibitor, indomethacine. The data strongly support that this novel purinoceptor may couple with PTX-sensitive G protein, Gi or Go, and the novel purinoceptor-mediated rat aorta smooth muscle contraction is dependent on the endogenous nitric oxide and prostaglandin synthesis. In an additional observation, pathophysiological conditions, such as hypertension, altered the characteristics of the novel receptor. Hypertension caused the novel receptor insensitive to adensone and uncoupling to PTX-sensitive G-proteins and lost of ability to initiate the receptor-mediated prostaglandin synthesis. All together, the novel putative endothelial purinoceptor may play an important role in the control of vascular tone in physiological or pathophysiological statues.

Key words: blood vessels, endothelium, purinoceptors, EDNO..

^f1To whom correspondence should be addressed: Tel.: 86-10-66932651; Fax: 86-10-6821-1656; E-mail:wh@nic.bmi.ac.cn

Received 29 November 2001; accepted 27 July 2002