title: Functional identification of adenylate cyclase-coupled adenosine receptors in rat brain microvessels.
abstract: It was investigated whether adenosine affects the adenylate cyclase system of microvessels, isolated from the rat cerebral cortex, via an external receptor recently classified as R-site receptor. Several adenosine analogs caused GTP-dependent stimulation of adenylate cyclase. The rank order of potency: NECA (5'-(N-ethylcarboxamido)-adenosine, EC50 0.2 microM) greater than adenosine (0.71 microM) = 2-chloroadenosine (0.72 microM) greater than L-PIA (N6-(L-phenylisopropyl)-adenosine, 1.03 microM) greater than D-PIA (N6-(D-phenylisopropyl)-adenosine, 5.27 microM) is consistent with that for agonism at activatory (Ra-site) adenosine receptors in other tissues. Adenylate cyclase stimulation by PIA displayed stereoselectivity. The action of NECA was competitively antagonized by 8-phenyltheophylline. These findings provide functional evidence for Ra-site adenosine receptors in rat brain microvessels. However, direct identification of these receptors by binding studies was not possible. Binding of [3H]NECA to rat brain microvessels displayed rapid on-off kinetics and saturability, but equivocal specificity.
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis*; D011983:Receptors, Purinergic
chemical_list: D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D019830:Adenosine-5'-(N-ethylcarboxamide); D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D000241:Adenosine