Evidence for the involvement of central 5-HT7 receptors in the micturition reflex in anaesthetized female rats.
(1) The effects of the selective 5-HT7 receptor antagonists SB-269970 (3-300 microg kg-1; n=5-6) and SB-656104 (30 microg kg-1; n=5) administered centrally (i.c.v.) were investigated on the 'micturition reflex' in the urethane anaesthetized female rat. (2) In cystometric recordings, SB-269970 caused significant increases in volume of 58+/-15 and 138+/-33% and pressure of 140+/-46 and 149+/-60% thresholds at 10 and 30 microg kg-1. These changes were associated with significant decreases in distension-induced bladder contraction of 62+/-14 and 60+/-11%, respectively. However, there was no change in residual volume. At the higher doses, SB-269970 blocked the micturition reflex. SB-656104 had similar effects to SB-269970 but in addition significantly increased the residual volume. (3) SB-269970 (10 microg kg-1; n=5) given i.v. had no effect on the micturition reflex. (4) SB-269970 (30 microg kg-1; n=4) given intrathecally (i.t.) had no effect on micturition reflex, although the selective 5-HT1A receptor antagonist WAY-100635 given i.t. after SB-269970 caused a significant increase in the volume threshold. (5) Using an isovolumetric method in which urethral changes were measured, SB-269970 (30 microg kg-1; n=4; i.c.v.) failed to have any effect on these urethral-evoked changes although they significantly reduced the amplitude of the bladder contraction. (6) These data demonstrate that 5-HT7 receptors located supraspinally in the rat are involved in the control of micturition.
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Kate E
KE
Department of Pharmacology, University College London, Royal Free Campus, Hampstead, London NW3 2PF.
Sanger
Gareth J
GJ
Ramage
Andrew G
AG
D000758:Anesthesia / Q000379:methods; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014554:Urination / Q000187:drug effects / Q000502:physiology*
D018686:Anesthetics, Intravenous; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor