title: Doxazosin selectively potentiates contraction to serotonin via 5-HT₂A receptors in longitudinal muscle strips of the rabbit gastric body.
abstract: The aims of this study were to examine the effects of doxazosin on contractile responses to 5-hydroxytryptamine (5-HT), carbachol, and histamine, and to compare them with those of prazosin, alfuzosin, and terazosin, and then characterize a pharmacological profile of the 5-HT-induced contractile response using preparations of isolated longitudinal muscle strips from the rabbit gastric body. The results from these preparations showed that the contraction response to 5-HT, but not to carbachol or histamine, was found to be dose-dependently potentiated by doxazosin and its enantiomers. The specific potentiation effect on 5-HT was not observed in the preparations that were treated with prazosin, terazosin, or alfuzosin. The contractile response to 5-HT and its potentiation by doxazosin were not affected by treatment with phenoxybenzamine. However, 5-HT-induced contraction was competitively antagonized by nefazodone (with pA₂ value of 8.64 ± 0.17), and was almost completely inhibited by treatment with indomethacin. In conclusion, doxazosin, but not prazosin, alfuzosin, or terazosin, selectively potentiates 5-HT-induced contraction in the rabbit gastric body strips via an α₁-adrenoceptor-independent mechanism, without chiral recognition of its enantiomers. Additionally, the contraction to 5-HT was found to be mediated via 5-HT(₂) receptors, and was similar to PGs synthesis in the preparations.
authors.affiliation: a Department of Pharmacology, Institute of Chinese Integrative Medicine, Hebei Medical University, 361 East Zhong-shan Road, Shijiazhuang 050017, Hebei, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xue-Bin
authors.initials: XB
authors.lastname: Cao
authors.forename: Lei-Ming
authors.initials: LM
authors.lastname: Ren
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017292:Doxazosin / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism; D013270:Stomach / Q000187:drug effects* / Q000502:physiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D017292:Doxazosin