A Subtype of the γ-Aminobutyric AcidBReceptor Regulates Cholinergic Twitch Response in the Guinea Pig Ileum11This work was supported by an Italian MURST Network grant (1997).

The pharmacological profile of the γ-aminobutyric acid (GABA)Breceptor regulating cholinergic twitch contraction in the guinea pig ileum myenteric plexus-longitudinal muscle preparation was investigated. GABA and (−)-baclofen inhibited the contraction, exhibiting quite close potencies (pD2for GABA = 5.70; pD2for (−)-baclofen = 5.33). The compound CGP 47656 also reduced the cholinergic twitch concentration (pD2= 5.42), but its efficacy was significantly lower than that of (−)-baclofen or GABA. Added at varying concentrations, CGP 47656 modified the concentration-response curve of (−)-baclofen as expected for a partial agonist. Phaclofen, CGP 36742, CGP 35348, and CGP 52432 behaved as competitive antagonists of (−)-baclofen, exhibiting the following pA2values: 3.90, 4.88, 5.02, and 7.82, respectively. The compound CGP 56999 behaved as a potent noncompetitive GABABreceptor antagonist. In comparing the pharmacological profile of the ileal receptor with those of the previously characterized pharmacological subtypes of the GABABreceptor present in the central nervous system, it can be seen that the GABABreceptor inhibiting cholinergic twitch contraction in guinea pig ileum myenteric plexus-longitudinal muscle mostly resembles the receptor located on somatostatin human neocortex nerve terminals.