Premium
Enhanced Transcription of Contractile 5‐Hydroxytryptamine 2A Receptors via Extracellular Signal‐Regulated Kinase 1/2 after Organ Culture of Rat Mesenteric Artery
Author(s) -
Cao YongXiao,
He LangChong,
Xu CangBao,
Luo GuoGang,
Edvinsson Lars
Publication year - 2005
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2005.pto960402.x
Subject(s) - ketanserin , contraction (grammar) , receptor , receptor antagonist , extracellular , biology , endocrinology , medicine , signal transduction , 5 ht receptor , mesenteric arteries , vascular smooth muscle , antagonist , artery , serotonin , pharmacology , microbiology and biotechnology , smooth muscle
5‐Hydroxytryptamine (5‐HT) has been found to elicit enhanced contractile effects in some vascular disorders. The present study was designed to examine if vascular 5‐HT 2A receptors are up‐regulated during organ culture and if the extracellular signal‐regulated protein kinase 1/2 (ERK1/2) pathways are involved. Compared with fresh rat mesenteric artery ring segments, the contractile responses to 5‐HT were significantly increased in the segments cultured for 6, 24 or 48 hr (P<0.05, P<0.01, P<0.01, respectively). The 5‐HT‐induced contraction occurred via 5‐HT 2A receptors, since the selective 5‐HT 2A antagonist ketanserin blocked the 5‐HT‐induced contraction in the fresh segments with a pA 2 value 9.5 (slope was 0.98 with 95% confidence intervals from 0.8 to 1.1). A similar result was obtained in the segments cultured for 24 hr with a pA 2 value of 9.43 (slope=0.91 and 95% confidence intervals between 0.45 to 2.3). In addition, the enhanced 5‐HT 2A receptor contraction occurred with a significant increase of 5‐HT 2A receptor mRNA (P<0.05). Organ culture of the mesenteric artery was found to activate ERK1/2 already within 1 and 3 hr. It is likely that the ERK1/2 pathways were involved as a initial switch, since the selective ERK1/2 pathway inhibitor SB386023 abolished both up‐regulation of 5‐HT 2A mRNA transcription and the enhanced contractile response to 5‐HT. These data reveal a role of ERK1/2 in up‐regulation of 5‐HT 2A receptors and suggest a possibility to inhibit the enhanced responses to 5‐HT by inhibition of the ERK1/2 pathway.