Abstract

The pharmacological profile of the γ-aminobutyric acid (GABA)_B receptor 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 (pD₂ for GABA = 5.70; pD₂ for (−)-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 pA₂ values: 3.90, 4.88, 5.02, and 7.82, respectively. The compound CGP 56999 behaved as a potent noncompetitive GABA_B receptor antagonist. In comparing the pharmacological profile of the ileal receptor with those of the previously characterized pharmacological subtypes of the GABA_B receptor present in the central nervous system, it can be seen that the GABA_B receptor inhibiting cholinergic twitch contraction in guinea pig ileum myenteric plexus-longitudinal muscle mostly resembles the receptor located on somatostatin human neocortex nerve terminals.