GABAB RECEPTOR MEDIATED INHIBITION OF FIELD STIMULATION INDUCED CONTRACTIONS OF DETRUSOR MUSCLE STRIPS FROM NEWBORN RATS

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Abstract
The effect of GABA on field stimulation (0.1 Hz)-induced contractions was 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 .times. 10-7 M) in both age groups. Atropine (3 .times. 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 adult rats. 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 .times. 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 .times. 10-7 M) induced contractions of detrusor of strips from newborn rats, while atropine (3 .times. 10-6 M) completely suppressed them. The 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.