Recombinant saphenous vein 5‐HT1B receptors of the rabbit: comparative pharmacology with human 5‐HT1B receptors

• Published in: British journal of pharmacology 1997-01, Vol.120 (1), p.153-159
• Main Authors: Wurch, Thierry, Palmier, Christiane, Colpaert, Francis C, Pauwels, Petrus J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood vessels and receptors; Cell Line; Colforsin - pharmacology; cyclic AMP; Cyclic AMP - biosynthesis; Fundamental and applied biological sciences. Psychology; Haplorhini; human 5‐HT1B receptor; Humans; ketanserin; Muscle, Smooth, Vascular - metabolism; Polymerase Chain Reaction; Rabbit recombinant saphenous vein 5‐HT1B receptor; Rabbits; rat C6‐glial cell line; Rats; Receptors, Serotonin - biosynthesis; Receptors, Serotonin - drug effects; Receptors, Serotonin - genetics; Recombinant Proteins - biosynthesis; Saphenous Vein - metabolism; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Transfection; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0700868

The rabbit recombinant saphenous vein 5‐hydroxytryptamine1B (rb 5‐HT1B) receptor stably transfected in rat C6‐glial cells was characterized by measuring adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) formation upon exposure to various 5‐HT receptor ligands. The effects of agonists and antagonists were compared with their effects determined previously at the human cloned 5‐HT1B (h 5‐HT1B) receptor under similar experimental conditions. Intact C6‐glial cells expressing rb 5‐HT1B receptors exhibited [3H]‐5‐carboxamidotryptamine (5‐CT) binding sites with a Kd of 0.80±0.13 nm and a Bmax between 225 to 570 fmol mg−1 protein. The binding affinities of a series of 5‐HT receptor ligands determined in a membrane preparation with [3H]‐5‐CT or [3H]‐N‐[4‐methoxy‐3‐(4‐methylpiperazin‐1‐yl)phenyl]‐3‐methyl‐4‐(4‐pyridyl)benzamide (GR 125,743) were similar. With the exception of ketanserin, ligand affinities were comparable to those determined at the cloned h 5‐HT1B receptor site. rb 5‐HT1B receptors were negatively coupled to cyclic AMP formation upon stimulation with 5‐HT agonists. Of the several 5‐HT agonists tested, 5‐CT was the most potent, the potency rank order being: 5‐CT>5‐HT>zolmitriptan>naratriptan>rizatriptan>sumatriptan>R(+)‐8‐(hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT). The maximal responses of these agonists were similar to those induced by 5‐HT. The potency of these agonists showed a positive correlation (r2=0.87; P