Brain α7 nicotinic receptor stimulation inhibits the rat micturition reflex via brain GABA<sub>A</sub> receptors

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  • Shimizu Yohei
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ. Ctr. Innov. and Translational Med., Kochi Med. Sch., Kochi Univ.
  • Shimizu Takahiro
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ.
  • Ono Hideaki
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ. Ctr. Innov. and Translational Med., Kochi Med. Sch., Kochi Univ.
  • Zou Suo
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ.
  • Yamamoto Masaki
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ.
  • Hata Yurika
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ. Ctr. Innov. and Translational Med., Kochi Med. Sch., Kochi Univ.
  • Aratake Takaaki
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ. Research Fellow of Japan Society for the Promotion of Science
  • Shimizu Shogo
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ.
  • Higashi Youichirou
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ.
  • Saito Motoaki
    Dept. of Pharmacol., Kochi Med. Sch., Kochi Univ.

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Other Title
  • 脳内α7型ニコチン受容体刺激はGABA<sub>A</sub>受容体を介して排尿を抑制する

Abstract

<p>We recently reported that intracerebroventricularly (icv) administered epibatidine (EP), a nicotinic receptor (nAChR) agonist, inhibited the rat micturition reflex. We examined brain mechanisms of the EP-induced inhibition focusing on α4β2 and α7 nAChRs and GABA receptors in urethane-anesthetized (0.8 g/kg, ip) male Wistar rats (300-400 g). A catheter was inserted into the bladder to perform cystometrograms (CMG, 12 ml/h saline infusion). Three hours after the surgery, mecamylamine (MEC, an nAChR antagonist, 100 or 300 nmol/rat), DHβE (an α4β2 nAChR antagonist, 100 or 300 nmol/rat), MLA (an α7 nAChR antagonist, 30 or 100 nmol/rat） or SR95531 (SR, a GABAA receptor antagonist, 0.1 nmol/rat) was icv pretreated 30 min before EP administration (1 nmol/rat, icv). Effects of PHA568487 (PHA, an α7 nAChR agonist, 0.3 or 1 nmol/rat, icv) on the micturition reflex were also evaluated. Icv administered EP prolonged intercontraction intervals (ICI), an index of micturition frequency. The EP-induced prolongation was attenuated by pretreatment with MEC, MLA and SR, but not with DHβE. Similar to EP, PHA also prolonged ICI. These results suggest that brain α7 nAChR stimulation inhibits the rat micturition reflex via brain GABAA receptors.</p>

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