Effects of gamma-aminobutyric acid agonists on the isolated perfused rat kidney.
The effects of gamma-aminobutyric acid (GABA) agonists were studied in the isolated perfused rat kidney. Perfusions were performed at constant flow with modified Ringer-Krebs solution. The GABAA agonist muscimol (0.1-75 microM) induced an increase in fractional excretion of water and sodium without promoting hemodynamic changes. These tubular changes were inhibited by atropine pretreatment. Thus, a possible modulation of tubular transport mechanisms via GABAA receptors acting on cholinergic system could be suggested. Muscimol was unable to modify the renal vascular resistance either at basal conditions or in noradrenaline-pretreated preparations. However, the GABAA antagonist bicuculline (50 microM) evoked an increased perfusion pressure. Despite the speculation that endogenous GABA could result in a maximal activation of these GABAergic processes, nonspecific binding sites for bicuculline should be considered. The GABAB agonist baclofen (0.05-500 microM) elicited a raised perfusion pressure and diminished glomerular filtration rate, accompanied by an increment in fractional excretion of water, sodium and glucose. These findings suggest a major GABAB receptor-mediated vasoconstriction at the afferent arteriole level. Proximal tubular structures seem to be a biological target for baclofen. GABA (0.05-1000 microM) evoked changes similar to those described for baclofen, although the glomerular filtration rate was not diminished. Data from this study indicate that the GABA system may be involved in the modulation of rat renal function.
Monasterolo
L A
LA
Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
Trumper
L
L
Elías
M M
MM
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D001640:Bicuculline