Coexpression of 5-HT2A and 5-HT4 receptors coupled to distinct signaling pathways in human intestinal muscle cells.
OBJECTIVE
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.
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000378:metabolism*; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction; D062366:para-Aminobenzoates
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D062366:para-Aminobenzoates; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; D044422:Receptors, Serotonin, 5-HT4; D015544:Inositol 1,4,5-Trisphosphate; D007650:Ketanserin; D000242:Cyclic AMP; D010129:4-Aminobenzoic Acid