Pharmacological characterisation of a cloned dog 5-HT1B receptor cell line.
In this study, the binding of [3H]5-HT to the cloned dog 5-hydroxytryptamine1B (dog 5-HT1B) receptor, stably expressed in Chinese hamster ovary cells (ATCC CCL 61)(CHO-K1), was characterised and its pharmacology compared with that of the cloned human and rat 5-HT1B receptors. [3H]5-HT specifically labeled, with high affinity, an apparently homogeneous population of binding sites in the dog 5-HT1B receptor cell line yielding a pKd of 8.1. [3H]5-HT inhibition and agonist-induced [35S] guanosine 5'[gamma-thio] triphosphate ([35S]GTPgammaS) binding studies revealed comparable results with the human but not the rat 5-HT1B receptor. In all three recombinant receptor cell lines, methiothepin displayed inverse agonism and GR127935 (N-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide) weak partial agonism.
Beer
M S
MS
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Heald
M A
MA
McAllister
G
G
Stanton
J A
JA
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D004285:Dogs; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008719:Methiothepin / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013462:Sulfur Radioisotopes; D014316:Tritium
C470302:HTR1B protein, human; D010069:Oxadiazoles; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D011993:Recombinant Fusion Proteins; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013462:Sulfur Radioisotopes; D014316:Tritium; C090701:GR 127935; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008719:Methiothepin