Effects of Adenosine and its Analogues on Porcine Basilar Arteries: Are Only A₂ Receptors Involved?

Abstract

Summary: The aim of this study was to test the effect of adenosine and four of its analogues, 5'-(N-ethyl)carbox amidoadenosine (NECA), 2-chloroadenosine (2-CADO), L-phenylisopropyladenosine (L-PIA), and N6-cyclohexyl adenosine (CHA), on prostaglandin (PG) F2u-constricted pig basilar arteries, and from their rank order of potency determine the receptor type involved, The order of po tency for the relaxation of the PGF2u constriction was NECA > adenosine, 2-CADO > L-PIA > CHA, which is Adenosine has been shown to dilate cerebral ar teries both in situ (Berne et aI., 1974) and in vitro (Hardebo and Edvinsson, 1979). It is known that the effects of adenosine are caused by an action on specific receptors found on the cell surface (Schwabe, 1981). The receptors can be subdivided into two classes: the Al (or R) receptor, a high-af finity receptor that is coupled to adenylate cyclase in an inhibitory manner (van Calker et aI., 1979; Londos et aI., 1980); and the A2 (or Ra) receptor, a low-affinity receptor that is coupled to adenylate cyclase in a stimulatory manner (Bruns, 1980). These receptors show a different affinity for adeno sine and its structural analogues, as has been shown by Londos et al. (1978) and Tr ost and Stock (1977) for the Al subtype and by Bruns (1980) for the A2 subtype. Previous work carried out suggests that the receptor involved in the vasodilatation of both peripheral (Kusachi et aI., 1983;Mustafa and Askar, 1985) and cerebral (Edvinsson and Fred holm, 1983) 40in keeping with the A2 receptor subtype, The study also investigated the effects of a known adenosine antagonist, namely, the xanthine derivative 8-phenyltheophylline, which at concentrations having no intrinsic effect (10-8 and 10-7 M) produced a significant shift to the right only for the NECA dose-response curve, Key Words: Adeno sine-Adenosine analogues-8-Phenyltheophylline Pig basilar artery -A2 Receptor.shown that adenosine-induced relaxation of cere bral arteries in a number of species was endothe lium independent; i.e., the action of adenosine on cerebral vessels is not dependent on the endothe lium being intact (Hardebo et aI., 1985).The aim of this study was to identify the re ceptors involved in the dilatation of the pig basilar artery and also to examine the antagonistic proper ties of 8-phenyltheophylline at concentrations that have no intrinsic etfect. MATERIALS AND METHODSSpecimens of basilar artery were obtained from adult pigs immediately after slaughter and stored in the bathing medium (see below) at 4°C until use. It was found that the responsiveness of the vessels was not affected by the length of time that they were stored at 4°C. The vessels were trimmed to a length of 4 mm and the segments were suspended between two L-shaped metal hooks in a vessel bath containing 20 ml of the bathing medium, which was being continuously gassed with 5% COz in oxygen, in both the stock solution and the bath, to produce a re sulting pH of between 7.35 and 7.45. The temperature of the bathing medium was kept constant at 37°C....

The Role of Adenosine in the Vascular Adaptation of Neonatal Cerebral Blood Flow during Hypotension

“…These data suggest indirectly that the effect of 8-PT on CBF during hypotension was mainly due to the antagonism of the adenosine receptors located on the smooth muscle cells of the cerebral vessels (McBean et al, 1988).…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…It has been claimed that human cerebral microvessels express A 2 , but not A 1 , receptors (Kalaria and Harik, 1988). A 2 receptors have also been described in porcine basilar arteries (McBean et al, 1988), goat cerebral vessels (Torregrosa et al, 1990b), and rat pial arterioles (Ibayashi et al, 1991). Both A 2A and A 2B receptors were later identified on vascular smooth muscle, mediating vasodilation in rat cerebral cortex (Coney and Marshall, 1998;Shin et al, 2000a).…”

Effects of Adenosine and Its Analogues on Isolated Internal Carotid Arteries from Newborn and Adult Pigs

“…These studies demonstrate that 5'-substituted analogues of adenosine are more po tent than N6-substituted adenosine ana logues in relaxing the vessels and suggest that the vasorelaxant activity of adenosine is ex erted through a stimulation of A2 receptors. The data on the relative potency of adeno sine to /-PIA are variable [5,16] and could be related to differences in the type of blood vessel and species studied.…”