Functional alteration of the GABAB receptor in the brain of spontaneously hypertensive rats.
1. We studied the ontogenetic development of GABAB receptors and their coupling to cyclic AMP formation in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rat brains. GABAB receptor binding to various brain regions was compared in age-matched SHR and WKY rats. 2. The specific [3H]-GABA binding to the posterior hypothalamus (PH) was significantly lower in not only 4 week old (normotensive) but also 11 week old (hypertensive) SHR, when compared with age-matched WKY. 3. Moreover, GABAB receptor agonists (baclofen and DN-2327)-induced suppression of adenylate cyclase activity also showed a decrease in 4 week old and 11 week old SHR PH. 4. We concluded that the number and the functional responsiveness of GABAB receptors in rat brains decrease in SHR, preceding blood pressure elevation. The activity of GABABergic mechanisms may be different in the brains of SHR and WKY rats.
Ichida
T
T
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Sasaki
S
S
Takeda
K
K
Kuriyama
K
K
Nakagawa
M
M
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018080:Receptors, GABA-B / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000201:enzymology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases