Influence of 5-HT1 receptor agonists on feline stomach relaxation

Abstract

Sumatriptan is known for its stomach relaxing properties in both humans and cats, but the receptor involved has not been characterized. In a barostat study the intragastric volume was monitored in sedated cats at constant pressure. The maximum intragastric volume increase after subcutaneous or intravenous administration of saline or agonists was registered [mean (n=4-5)]. Sumatriptan (0.01-1 mg kg(-1)) induced a dose-dependent intragastric volume increase vs. saline (4-15 vs. 5 ml, respectively) that was sometimes accompanied by retching after 8-10 min. Pre-treatment with nitric oxide-synthase inhibitors and different 5-HT(1) receptor antagonists N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide(WAY-100635), 2-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic-acid[4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]amide(GR-127935), N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan-amide(5-HTP-DP) and 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine-HCl(NAN-190) did not affect the sumatriptan-induced effect. Alniditan (5-HT(1A/1D) receptor agonist) and flesinoxan (5-HT(1A) receptor agonist) did not induce significant intragastric volume changes. The 5-HT(1F) receptor agonists 5-hydroxy-3-(1-methylpiperidin-4-yl)-1H-indole(BRL-54443) and (R)-(+)-N-(3-dimethylamino-1,2,3,4-tetrahydro-9H-carbazol-6-yl)-4-fluorobenzamide(LY-344864; 0.003-3 mg kg(-1)) however induced a dose-dependent intragastric volume increase (6-36 and 5-26 ml, respectively), no retching was seen. Our results suggest that stimulation of 5-HT(1F) receptors induces feline stomach relaxation. Whether the sumatriptan-induced gastric relaxation in cats is due to interaction with 5-HT(1F) receptors could not be proven absolutely in view of the lack of selective 5-HT(1F) receptor antagonists.