guanosine-triphosphate and tryptamine

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.

Topics: 5-Methoxytryptamine; 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Bufotenin; Cell Line; Dibenzylchlorethamine; Dose-Response Relationship, Drug; GTP-Binding Proteins; Guanosine Triphosphate; Indoles; Inositol Phosphates; Kinetics; Mammary Neoplasms, Experimental; Mathematics; N,N-Dimethyltryptamine; Piperazines; Quipazine; Rats; Receptors, Serotonin; Sugar Phosphates; Tetrahydronaphthalenes; Tryptamines