GABA-A agonist muscimol inhibits stimulated vasopressin release in the posterior pituitary of Sprague-Dawley, Wistar, Wistar-Kyoto and spontaneously hypertensive rats.
Vasopressin-containing neurosecretory cells are partly regulated by GABAergic neurons present both at the hypothalamic and the pituitary level. In the present work, we compared GABA effects on vasopressin release from posterior pituitaries of Sprague-Dawley (SPD), Wistar (W), Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Release of vasopressin was studied in vitro by placing neurointermediate lobes in perfusion chambers. It was stimulated twice by 50 mM KCl (S1 and S2) and the ratio between the first and the second stimulation was calculated (S2/S1). The basal and stimulated release of vasopressin was enhanced in the SHR. There was no difference in vasopressin content in the pituitary between the WKY and the SHR but the levels were lower compared to the SPD rat. Muscimol, a GABA-A receptor agonist, was added during S2. Muscimol inhibited in a dose-dependent manner the stimulated release of vasopressin, with an ED50 about 3 microM. The effect of muscimol was not statistically different between the strains expressed in ratios. The actual inhibition was apparently greater in the SHR, as both basal and stimulated vasopressin release was larger.
Magnusson
A M
AM
Department of Medical Pharmacology, Uppsala University, Sweden.
Meyerson
B J
BJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D013045:Species Specificity; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D011963:Receptors, GABA-A; D014667:Vasopressins; D009118:Muscimol; D011189:Potassium Chloride