title: The 5-hydroxytryptamine (5-HT2) receptor stimulates inositol phosphate formation in intact and broken WRK1 cells: determination of occupancy-response relationships for 5-HT agonists.
abstract: 5-Hydroxytryptamine (5-HT) stimulates the accumulation of inositol-trisphosphate in WRK1 cells, a cell line originating from a rat mammary tumor. 5-HT acts via a single receptor type for which it has an affinity constant estimated to be 1.27 microM. A series of agonists known to act at 5-HT2 receptors are partial agonists in this system and have a rank order of relative intrinsic efficacies corresponding to that seen in other systems possessing 5-HT2 receptors. There is an essentially linear occupancy-response relationship for 5-HT and other agonists indicating the absence of a strong amplification mechanism between receptor activation and inositol phosphate formation. The selective blockade of the 5-HT response by nanomolar concentrations of 5-HT2 selective antagonists but not by drugs acting at other 5-HT receptor subtypes suggest that the receptor in WRK1 cells is of the 5-HT2 type. Additionally, we demonstrate that in WRK1 membranes 5-HT acts via the 5-HT2 receptor to elicit a GTP dependent increase in the production of inositol-bisphosphate and inositol-trisphosphate. These properties of the WRK1 cell line indicate that it is a useful model with which to study the nature of 5-HT receptor coupling to the putative second messenger(s), the inositol phosphates.
mesh_terms: D008735:5-Methoxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002027:Bufotenin / Q000494:pharmacology; D002460:Cell Line; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008433:Mathematics; D004130:N,N-Dimethyltryptamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D013403:Sugar Phosphates / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
chemical_list: D007211:Indoles; D007295:Inositol Phosphates; D010879:Piperazines; D011985:Receptors, Serotonin; D013403:Sugar Phosphates; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; D002027:Bufotenin; C018406:1-(3-trifluoromethylphenyl)piperazine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D008735:5-Methoxytryptamine; C030820:tryptamine; D003983:Dibenzylchlorethamine; D011814:Quipazine; C035668:N-methyltryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D004130:N,N-Dimethyltryptamine