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Smooth muscle layer‐dependent distribution of 5‐hydroxytryptamine 7 receptor in the porcine myometrium
Author(s) -
Kitazawa Takio,
Yamada Yuko,
Iwano Hidetomo,
Yokota Hiroshi,
Yuasa Akira,
Taneike Tetsuro
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703290
Subject(s) - ibmx , forskolin , endocrinology , medicine , myometrium , contractility , adenosine , chemistry , contraction (grammar) , receptor , muscle contraction , carbachol , biophysics , biology , uterus
To analyse the mechanisms of muscle layer‐dependent inhibition of porcine myometrial contractility by 5‐hydroxytryptamine (5‐HT), the effects of 5‐HT, 5‐carboxamidotryptamine(5‐CT), 5‐methoxytryptamine (5‐MeOT), forskolin and cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) analogues on spontaneous and stimulant‐induced contractions were examined in longitudinal (LM) and circular muscles (CM). In addition, accumulation of cyclic AMP by 5‐HT and distribution of 5‐HT 7 receptors in LM and CM layers were compared using biochemical and molecular approaches. 5‐HT receptor agonists inhibited the spontaneous contractions of LM and CM (5‐CT>5‐HT>5‐MeOT), but CM was more sensitive than was LM. The inhibition by the agonists was antagonized by methiothepin (100 n M ). Carbachol‐, high‐K + ‐, histamine‐ and Ca 2+ ‐induced contractions were inhibited by 5‐HT with different responsivenesses (CM>LM). Even in the presence of 3‐isobutyl‐1‐methylxanthine (IBMX), the inhibition by 5‐HT in the CM was still more conspicuous than that in the LM. Compared with the CM, the inhibition of spontaneous contraction by forskolin, dibutyryl‐cyclic AMP and 8‐bromo‐cyclic AMP was marked in the LM. 5‐HT (1 n M –1 μ M ) increased the cyclic AMP in both muscle layers, but the increment in the CM was higher than that in the LM whether IBMX was present or not. LM and CM layers contained a single class of [ 3 H]‐5‐CT binding sites with a similar K d value (0.21–0.24 n M ). However, B max (5‐HT 7 receptor concentration) in the CM (120.6 fmol mg −1 protein) was higher than that in the LM (30.4 fmol mg −1 protein). The molecular study (reverse transcription polymerase chain reaction) demonstrated the expression of 5‐HT 7 receptor mRNA in the CM was higher than that in the LM. These results suggest that the muscle layer‐dependent difference in inhibition by 5‐HT is not restricted to spontaneous contraction but applies to various contractions in the porcine myometrium. Different inhibition of the contractility by 5‐HT is caused by muscle layer‐related accumulation of cyclic AMP (CM>LM), due to smooth muscle‐layer dependent distribution (CM>LM) of 5‐HT 7 receptors.British Journal of Pharmacology (2000) 130 , 79–89; doi: 10.1038/sj.bjp.0703290