Stimulation of brain α7-nicotinic acetylcholine receptors suppresses the rat micturition through brain GABAergic receptors

Yohei Shimizu; Takahiro Shimizu; Suo Zou; Hideaki Ono; Yurika Hata; Masaki Yamamoto; Takaaki Aratake; Shogo Shimizu; Youichirou Higashi; Takashi Karashima; Motoaki Saito

doi:10.1016/j.bbrc.2021.02.051

Stimulation of brain α7-nicotinic acetylcholine receptors suppresses the rat micturition through brain GABAergic receptors

Biochem Biophys Res Commun. 2021 Apr 9:548:84-90. doi: 10.1016/j.bbrc.2021.02.051. Epub 2021 Feb 23.

Authors

Affiliations

¹ Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan; Center for Innovative and Translational Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan.
² Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan. Electronic address: shimizu@kochi-u.ac.jp.
³ Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan.
⁴ Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan; Japan Society for the Promotion of Science, Japan.
⁵ Department of Urology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan.

PMID: 33636639
DOI: 10.1016/j.bbrc.2021.02.051

Abstract

Brain nicotinic acetylcholine receptors (nAChRs) reportedly suppress the micturition, but the mechanisms responsible for this suppression remain unclear. We previously reported that intracerebroventricularly administered (±)-epibatidine (non-selective nAChR agonist) activated the sympatho-adrenomedullary system, which can affect the micturition. Therefore, we investigated (1) whether intracerebroventricularly administered (±)-epibatidine-induced effects on the micturition were dependent on the sympatho-adrenomedullary system, and (2) brain nAChR subtypes involved in the (±)-epibatidine-induced effects in urethane-anesthetized male Wistar rats. Plasma noradrenaline and adrenaline (catecholamines) were measured just before and 5 min after (±)-epibatidine administration. Evaluation of urodynamic parameters, intercontraction intervals (ICI) and maximal voiding pressure (MVP) by cystometry was started 1 h before (±)-epibatidine administration or intracerebroventricular pretreatment with other drugs and continued 1 h after (±)-epibatidine administration. Intracerebroventricularly administered (±)-epibatidine elevated plasma catecholamines and prolonged ICI without affecting MVP, and these changes were suppressed by intracerebroventricularly pretreated mecamylamine (non-selective nAChR antagonist). Acute bilateral adrenalectomy abolished the (±)-epibatidine-induced elevation of plasma catecholamines, but had no effect on the (±)-epibatidine-induced ICI prolongation. The latter was suppressed by intracerebroventricularly pretreated methyllycaconitine (selective α7-nAChR antagonist), SR95531 (GABA_A antagonist), and SCH50911 (GABA_B antagonist), but not by dihydro-β-erythroidine (selective α4β2-nAChR antagonist). Intracerebroventricularly administered PHA568487 (selective α7-nAChR agonist) prolonged ICI without affecting MVP, similar to (±)-epibatidine. These results suggest that stimulation of brain α7-nAChRs suppresses the rat micturition through brain GABA_A/GABA_B receptors, independently of the sympatho-adrenomedullary outflow modulation.

Keywords: Alpha7-nicotinic acetylcholine receptors; Brain; GABA(A) receptors; GABA(B) receptors; Micturition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Medulla / drug effects
Adrenal Medulla / metabolism
Adrenalectomy
Animals
Brain / metabolism*
Bridged Bicyclo Compounds, Heterocyclic / pharmacology
Epinephrine / blood
Male
Muscle Contraction / drug effects
Norepinephrine / blood
Pyridines / pharmacology
Rats
Rats, Wistar
Receptors, GABA / metabolism*
Sympathetic Nervous System / drug effects
Sympathetic Nervous System / metabolism
Urination*
alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

Bridged Bicyclo Compounds, Heterocyclic
Pyridines
Receptors, GABA
alpha7 Nicotinic Acetylcholine Receptor
epibatidine
Norepinephrine
Epinephrine