Rabbit cerebral cortex 5HT1a receptors.
Selective 5HT1a agonist binding to membranes from rabbit cerebral cortex was concentration-dependent and saturable; the Kd was 1.1 nM and Bmax of 480 fmols/mg protein. Scatchard as well as Hill plots were linear; the Hill coefficient was 0.96, suggesting a single, non-interacting binding site. Agonist binding was inhibited in a concentration-dependent fashion by gamma S GTP, a result consistent with the coupling of this binding site to the G protein signal transduction system. In competition experiments involving agonist and a series of agents with known affinities and specificities at 5HT1a receptors, a rank order relationship was found consistent with this binding site being a 5HT1a binding site. Direct comparisons of agonist and antagonist binding at rat cerebral cortex 5HT1a receptors and cloned human 5HT1a receptors also suggested that the rabbit binding site belongs to the 5HT1a class. The only rank order anomalies were with methiothepin in rabbit cerebral cortex, where a comparatively high Ki was observed and with buspirone in cloned human 5HT1a receptor, where a low Ki was determined; these anomalies bear further study in light of the comparative pharmacology of 5HT1a receptors. Finally, the natural product parthenolide was tested for affinity in the rabbit, rat, and human systems, where it uniformly was unable to displace agonist, suggesting that the 5HT1a receptor is not a target for this compound. Overall, these results suggest that a functional 5HT1a receptor exists in rabbit cerebral cortex.
Weber
J T
JT
Department of Pharmaceutical Sciences, School of Pharmacy, University of Montana, Missoula 59812-1075, USA.
Hayataka
K
K
O'Connor
M F
MF
Parker
K K
KK
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive / Q000502:physiology; D016466:CHO Cells; D002540:Cerebral Cortex / Q000737:chemistry*; D006224:Cricetinae; D004146:Dioxanes / Q000037:antagonists & inhibitors; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000037:antagonists & inhibitors; D006801:Humans; D007700:Kinetics; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology; D013141:Spiro Compounds / Q000037:antagonists & inhibitors; D014316:Tritium
D004146:Dioxanes; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012717:Sesquiterpenes; D013141:Spiro Compounds; D014316:Tritium; C002669:parthenolide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol; C018387:spiroxatrine; D019204:GTP-Binding Proteins