Age-related development of gamma-aminobutyric acid (GABA)B receptor functions in various brain regions of spontaneously hypertensive rats.
The age-related development of GABAB receptors and their coupling to adenylate cyclase were studied in the brains of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Compared with WKY rats, the specific [3H]GABA binding to GABAB receptors showed a significant decrease not only in the posterior hypothalamus, midbrain, hippocampus and striatum of eleven-week-old SHR, which maintain a hypertensive state, but also in the posterior hypothalamus of four-week-old normotensive SHR. Similarly, the GABAB receptor agonists (baclofen and DN-2327)-induced suppression of adenylate cyclase activity showed a decrease in the posterior hypothalamus of four-week-old SHR as well as in the posterior hypothalamus and striatum of eleven-week-old SHR. These results suggest that the functions of the GABAB receptor in the brain of SHR may be decreased independently from the occurrence of blood pressure elevation and that such changes may even be involved in the pathogenesis of SHR.
Ichida
T
T
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Kuriyama
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism; D054833:Isoindoles; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018079:Receptors, GABA / Q000502:physiology*; D013141:Spiro Compounds / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018755:GABA Agonists; D054833:Isoindoles; D009287:Naphthyridines; D018079:Receptors, GABA; D013141:Spiro Compounds; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D001418:Baclofen; C060382:pazinaclone