GABAB receptor mediated inhibition of field stimulation induced contractions of detrusor muscle strips from newborn rats.
The effect of GABA on field stimulation (0.1 Hz) induced contractions have been examined on detrusor strips from adult and newborn rats. Field stimulation induced contractions were unaffected by hexamethonium (10(-5) M) but almost suppressed by tetrodotoxin (5 X 10(-7) M) in both age groups. Atropine (3 X 10(-6) M) produced a marked inhibition of twitches in detrusor strips from newborn rats but only a slight (10% or less) inhibition in strips from adult animals. Neither GABA (10(-4), homotaurine (10(-3) M) or (+/-)-baclofen (10(-4] affected twitches in detrusor strips from adults rats. On the other hand both GABA and (+/-)-baclofen inhibited, to about the same extent (55-60% inhibition) twitches in detrusor strips from newborn animals. Homotaurine had no significant effect. The effects of both GABA (10(-4) M) and (+/-)-baclofen (10(-4) M) on twitches in detrusor strips from newborn rats were reduced if the preparations were previously exposed to a low concentration of GABA (5 X 10(-6) M) thus indicating desensitization. The inhibitory effect of GABA on twitches in newborn rats were concentration dependent in the range of 10(-7) to 10(-4) M. The GABAA receptor antagonist picrotoxin (10(-4) M) had no effect on the GABA concentration response curve whereas the GABAB receptor antagonist, homotaurine, produced an antagonism of the competitive type. The calculated pA2 value for the GABA-homotaurine interaction was 4.4 +/- 0.07. Neither GABA (10(-4) M) nor (+/-)-baclofen (10(-4) M) produced any significant inhibition of acetylcholine (2 X 10(-7) M) induced contractions of detrusor of strips from newborn rats, while atropine (3 X 10(-6) M) completely suppressed them. These results indicate that GABA inhibits field stimulation induced contractions of detrusor strips from newborn rats by activating prejunctional receptors (presumably of the GABAB subtype) which inhibit the release of acetylcholine from the postganglionic nerve endings.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology*; D011963:Receptors, GABA-A; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects*
D001285:Atropine; D001418:Baclofen; D006584:Hexamethonium Compounds; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D013654:Taurine; D013779:Tetrodotoxin; C001355:tramiprosate