BACKGROUND & AIMS: The type and function of 5-hydroxytryptamine (5HT) receptors on intestinal muscle cells in humans are not known. 5-HT receptors were characterized pharmacologically and by radioligand binding. METHODS: Contraction, relaxation, inositol 1,4,5-triphosphate (IP3) and adenosine 3',5'-cyclic monophosphate (cAMP) formation, and 5-HT binding were measured in dispersed muscle cells and in cells in which only one receptor type was preserved by selective receptor protection. RESULTS: 5-HT binding was completely inhibited by 5-HT and partially by 5-HT2A (ketanserin), 5-HT4 (SDZ-205,557), and 5-HT1p (N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide; 5-HTP-DP) receptor antagonists. 5-HT caused contraction that was inhibited by ketanserin and augmented by SDZ-205,557 and 5-HTP-DP. In the presence of ketanserin, 5-HT caused relaxation of cholecystokinin-contracted cells that was inhibited by SDZ-205,557 and 5-HTP-DP. 5-HT increased IP3, which was inhibited by ketanserin, and cAMP, which was inhibited by SDZ-205,557 and 5-HTP-DP. In cells with only 5-HT2A receptors, 5-HT caused contraction only, and residual binding was inhibited by ketanserin. In cells with only 5-HT4/5-HT1p receptors, 5-HT caused only relaxation and residual binding was inhibited by SDZ-205,557 and 5-HTP-DP. CONCLUSIONS: 5-HT2A receptors mediating contraction and 5-HT4 receptors mediating relaxation coexist on human intestinal muscle cells. The 5-HT4 receptors are closely similar or identical to 5-HT1p receptors.
BACKGROUND & AIMS: The type and function of 5-hydroxytryptamine (5HT) receptors on intestinal muscle cells in humans are not known. 5-HT receptors were characterized pharmacologically and by radioligand binding. METHODS: Contraction, relaxation, inositol 1,4,5-triphosphate (IP3) and adenosine 3',5'-cyclic monophosphate (cAMP) formation, and 5-HT binding were measured in dispersed muscle cells and in cells in which only one receptor type was preserved by selective receptor protection. RESULTS: 5-HT binding was completely inhibited by 5-HT and partially by 5-HT2A (ketanserin), 5-HT4 (SDZ-205,557), and 5-HT1p (N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide; 5-HTP-DP) receptor antagonists. 5-HT caused contraction that was inhibited by ketanserin and augmented by SDZ-205,557 and 5-HTP-DP. In the presence of ketanserin, 5-HT caused relaxation of cholecystokinin-contracted cells that was inhibited by SDZ-205,557 and 5-HTP-DP. 5-HT increased IP3, which was inhibited by ketanserin, and cAMP, which was inhibited by SDZ-205,557 and 5-HTP-DP. In cells with only 5-HT2A receptors, 5-HT caused contraction only, and residual binding was inhibited by ketanserin. In cells with only 5-HT4/5-HT1p receptors, 5-HT caused only relaxation and residual binding was inhibited by SDZ-205,557 and 5-HTP-DP. CONCLUSIONS:5-HT2A receptors mediating contraction and 5-HT4 receptors mediating relaxation coexist on human intestinal muscle cells. The 5-HT4 receptors are closely similar or identical to 5-HT1p receptors.
Authors: N H Prins; N P Shankley; N J Welsh; M R Briejer; R A Lefebvre; L M Akkermans; J A Schuurkes Journal: Br J Pharmacol Date: 2000-04 Impact factor: 8.739
Authors: Arif Luqman; Patrick Ebner; Sebastian Reichert; Peter Sass; Clement Kabagema-Bilan; Christine Heilmann; Peter Ruth; Friedrich Götz Journal: Cell Microbiol Date: 2019-06-07 Impact factor: 3.715