A subtype of the gamma-aminobutyric acid(B) receptor regulates cholinergic twitch response in the guinea pig ileum.
The pharmacological profile of the gamma-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 (pD(2) for GABA = 5.70; pD(2) for (-)-baclofen = 5.33). The compound CGP 47656 also reduced the cholinergic twitch concentration (pD(2) = 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 pA(2) 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.
Marcoli
M
M
Dipartimento di Medicina Sperimentale, Sezione di Farmacologia e Tossicologia, Genova, Italy. marcoli@pharmatox.unige.it
Scarrone
S
S
Maura
G
G
Bonanno
G
G
Raiteri
M
M
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D018755:GABA Agonists; D018756:GABA Antagonists; D008024:Ligands; D018080:Receptors, GABA-B; C052329:phaclofen; D001418:Baclofen