The pharmacology and distribution of human 5‐hydroxytryptamine_2B (5‐HT_2b) receptor gene products: comparison with 5‐HT_2a and 5‐HT_2c receptors

Abstract

1 Full length clones of the human 5-HT2B receptor were isolated from human liver, kidney and pancreas. The cloned human 5-HT2B receptors had a high degree of homology (-80%) with the rat and mouse 5-HT2B receptors. 2 PCR amplification was used to determine the tissue distribution of human 5-HT2B receptor mRNA. mRNA encoding the 5-HT2B receptor was expressed with greatest abundance in human liver and kidney. Lower levels of expression were detected in cerebral cortex, whole brain, pancreas and spleen. Expression was not detected in heart. 3 Northern blot analysis confirmed the presence of 5-HT2B receptor mRNA (a 2.4 kB sized band) in pancreas, liver and kidney. An additional 3.2 kB sized band of hybridization was detected in liver and kidney. This raises the possibility of a splice variant of the receptor or the presence of an additional homologous receptor. On the basis of a higher affinity for ketanserin and a lower affinity for yohimbine the human 5-HT2B receptor also appeared to differ from the rat 5-HT2B receptor. 5 These findings confirm the sequence of the human 5-HT2B receptor and they demonstrate that the receptor has a widespread tissue distribution. In addition, these data suggest that there are differences in ligand affinities between different species homologues of the receptor. Finally, the finding of two distinct bands on the Northern blots of liver and kidney raises the possibility of splice variants or subtypes of 5-HT2B receptors, within these tissues.

Participation of 5‐HT1‐like and 5‐HT2A receptors in the contraction of human temporal artery by 5‐hydroxytryptamine and related drugs

“…All data are 5-HT, 5-HT2B and 5-HT2c (see Fozard & Kalkman, 1994). usually higher (pKD-6.7-7.6: Hoyer et al, 1985;Herndon et al, 1992;Bonhaus et al, 1995) than for 5-HT2B receptors (pKD-5.5-6.7: Loric et al, 1992;Wainscott et al, 1993;Bonhaus et al, 1995) in a variety of species including man (Bonhaus et al, 1995). In cell lines derived from mouse teratocarcinoma, 5-HT2B receptors are expressed during differentiation that have even relatively high affinity for ketanserin (pKD-7.2-7.4, Loric et al, 1995).…”

Immunohistochemical localisation of the serotonin 5‐HT2B receptor in mouse gut, cardiovascular system, and brain

“…Some pharmacological properties of antagonistic compounds such as yohimbine relate this pharmacology to that of the 5-HT1B-1D subfamily. The group of T. Blackburn reported the synthesis of a first generation of selective antagonist, the SB200646A compound which possess high affinity for 5-HT2B and 5-HT2C but not 5-HT2A nor any other receptor tested [5]. This compound acts on hypolocomotion, hypophagia and anxiogenic paradigms [6].…”

Metachlorophenylpiperazine (m-CPP) induced intracavernous pressure responses in anaesthetized rats

“…ICP responses resulting from direct stimulation of the CN (20 Hz, 2.5 V, 1 ms pulse width) were similar 10 Bonhaus et al, 14 Bigoni et al 41 and Paiva et al 42 m-CPP induced intracavernous pressure responses ES Hayes and PG Adaikan amongst treatment groups and ranged from 27 AE 4 mmHg to 41 AE 10 mmHg (P > 0.30). Preliminary dose-ranging studies using doses of m-CPP (0.1 -1.0 mg=kg; n ¼ 3), TFMPP (0.3 -3.0 mg=kg; n ¼ 3) and quipazine (0.3 -3.0 mg=kg; n ¼ 3) known to induce erection in conscious rats 3 indicated that m-CPP was the only drug to elicit CN and ICP responses in anesthetized rats at doses producing erection in conscious rats (data not shown).…”

“…12 TFMPP, quipazine and m-CPP display similar affinity for 5-HT 2c receptors and, similar potency and efficacy in stimulating IP 3 turnover in rat choroid plexus in vitro (a bioassay for 5-HT 2c agonists). 13 We have conducted an analysis of data presented by Hoyer et al 10 and Bonhaus et al 14 and have determined a strong correlation for the in vivo and in vitro potency of agonists and antagonists at 5-HT 2a =5-HT 2c receptors and binding affinities at native and cloned human and rat 5-HT 2a =5-HT 2c receptors (r ¼ 0.96-0.98; n ¼ 7; t ¼ 7.8 -15.3, t (0.05,5) ¼ 2.571; P < 0.001). Therefore, although complete dose -response curves were not examined in this study, doses were selected based on known in vivo and in vitro potency and selectivity at the various receptor subtypes and, preliminary experiments.…”