Evidence for Presynaptic Adenosine A2a Receptors Associated with Norepinephrine Release and Their Desensitization in the Rat Nucleus Tractus Solitarius

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Abstract
Rat medullary brain segments containing primarily nucleus tractus solitarius (NTS) were used for superfusion studies of evoked transmitter release and for isotherm receptor binding assays. Isotherm binding assays with [3H]CGS-21680 on membranes prepared from NTS tissue blocks indicated a single high-affinity binding site with a KD of 5.1 +/- 1.4 nM and a Bmax of 20.6 +/- 2.4 fmol/mg of protein. The binding density for [3H]CGS-21680 on NTS membranes was 23 times less than comparable binding on membranes from striatal tissue. Electrically stimulated (1 min at 25 mA, 2 ms, 3 Hz) release of [3H]norepinephrine ([3H]NE) from 400-microns-thick NTS tissue slices resulted in an S2/S1 ratio of 0.96 +/- 0.02. Superfusion of single tissue slices with 0.1-100 nM CGS-21680, a selective adenosine A2a receptor agonist, for 5 min before the S2 stimulus produced a significant concentration-dependent increase in the S2/S1 fractional release ratio that was maximal (31.3% increase) at 1.0 nM. However, superfusion of tissue slices with CGS-21680 over the same concentration range for 20 min before the S2 stimulus did not alter the S2/S1 ratio significantly from control release ratios. The augmented release of [3H]NE mediated by 1.0 nM CGS-21680 with a 5-min tissue exposure was abolished by 1.0 and 10 nM CGS-15943 as well as by 100 nM 8-(3-chlorostyryl)caffeine, both A2a receptor antagonists, but not by 1.0 nM 8-cyclopentyl-1,3-dipropylxanthine, the A1 receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

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