| Abstract: | In the present study we set out to define, using discriminatory agonists and antagonists, the adenosine receptors modulating sympathetic neurotransmission in the rat kidney. Isolated kidneys from male Wistar rats were perfused with modified Krebs-Henseleit buffer solution at constant flow. The neuronal noradrenaline stores were labeled with 3H-noradrenaline and the renal nerves stimulated electrically (2 Hz, 3 msec, 9 mA, during 20 sec at intervals of 6 min). 3H overflow was taken as an index of 3H-noradrenaline release. The A1 receptor selective agonists N6-cyclopentyladenosine (CPA), N6-cyclohexyladenosine (CHA), and N6-[R(−)-1-phenyl-2-propyl]adenosine (R-PIA), and the mixed A1/A2A receptor agonists 5′-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CADO) inhibited evoked 3H outflow concentration-dependently. The selective A2A receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5′-N-ethylcarboxamidoadenosine (CGS 21680), at concentrations selective for A2A receptors, failed to modify 3H outflow, whereas at higher concentrations it induced inhibition. The rank order of potency of agonists, CPA > CHA = R-PIA > NECA > CADO >> CGS 21680, is typical for an interaction with the A1 receptor. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), at concentrations selective for blockade of A1 receptors, blocked concentration-dependently the inhibitory effects of CPA and NECA; no evidence of an increase in outflow was seen with NECA in the presence of DPCPX. The selective A2A receptor antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazol[1,5-c] quinazoline-5-amine (CGS 15943) did not influence the agonist effects at concentrations interacting selectively with A2A receptors but antagonized them concentration-dependently at higher, non-selective concentrations. Taken together, our data establish the presence of inhibitory adenosine A1 receptors on the terminal sympathetic neurons of rat kidney. No evidence was obtained for the presence of functional A2A receptors in this preparation. © 1996 Wiley-Liss, Inc. |
