Comparison of [3H]baclofen binding to GABAB receptors in spontaneously hypertensive and normotensive rats.
Baclofen-sensitive GABAB receptor binding to various brain regions was compared in age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rat. The specific [3H]baclofen binding was significantly higher in SHR cerebellum, hippocampus and nucleus tractus solitarii (NTS), but lower in medulla, when compared with WKY. Scatchard analysis of the binding isotherms indicated a higher Bmax of the high affinity sites in SHR cerebellum and hippocampus and a lower Bmax of the same sites in SHR medulla. Guanyl nucleotide (GTP) decreased [3H]baclofen binding in brain regions of SHR and WKY, although the percentage inhibition of binding did not differ between SHR and WKY. The basal adenylate cyclase activity in SHR cerebellum was lower, in contrast to higher [3H]baclofen binding, whereas lower baclofen binding in SHR medulla was accompanied with higher adenylate cyclase activity. (+/-)Baclofen inhibited adenylate cyclase activity in both SHR and WKY rat brain. Among various regions, the percentage inhibition of cyclase activity in SHR cerebellum was significant lower, as compared to WKY cerebellum. These results suggest that activity of GABABergic mechanisms may be different in SHR and WKY rat brain.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011963:Receptors, GABA-A / Q000378:metabolism*
D011963:Receptors, GABA-A; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D001418:Baclofen