Enhancing and inhibitory effects of H2-receptor antagonists on the GABA and the GABAA-agonist muscimol responses of the isolated guinea pig ileum: a pharmacodynamic interaction.
This study investigates the effect of histamine H(2)-receptor antagonists on the GABA-responses of the intestine. GABA and the GABA(A)-agonist muscimol were applied to isolated ileal guinea pig preparations in the absence, and presence of two H(2)-receptor antagonists, famotidine and cimetidine. Both GABA and muscimol produced a concentration-dependent contractile effect on the guinea pig ileum. Famotidine and cimetidine modified this contractile effect, either by enhancing or by inhibiting it. The differing results depended not only on the antagonist concentration, but also on the concentration of GABA or muscimol. When tested at the concentration of 10(-5)M, famotidine enhanced the contractile response of the ileum to either GABA or muscimol, while cimetidine did not modify it. At the concentration of 3 x 10(-4)M, both H(2)-receptor antagonists tested inhibited the contractile effect of either GABA or muscimol. However, the famotidine-induced inhibition was more potent than the one produced by cimetidine. In conclusion, the interaction of H(2)-receptor antagonists with GABA receptors is not limited to the central nervous system, but it also extends to the peripheral nervous system. The receptor interaction mainly involves GABA(A)-receptors and depends on both the specific H(2)-antagonist and the concentration used.
Koutsoviti-Papadopoulou
Maria
M
Laboratory of Pharmacology, School of Veterinary Medicine, Aristotle University, Thessaloniki 54124, Greece. mariakp@vet.auth.gr
Nikolaidis
Efstathios
E
Kounenis
Georgios
G
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015738:Famotidine / Q000494:pharmacology*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D006635:Histamine H2 Antagonists; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D015738:Famotidine; D002927:Cimetidine