Effect of Muscarinic Receptor Modulators in the Hypothalamic Supraoptic Nucleus of the Rat.
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概要
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Muscarinic antagonists were injected into the hypothalamic supraoptic nucleus (SON) and their effects on the acetylcholine (ACh) release of this nucleus were studied by in vivo microdialysis techniques. Atropine, AF-DX116 (a M<SUB>2</SUB>-receptor antagonist), 4-DAMP (a M<SUB>3</SUB>-receptor antagonist) and pirenzepine (a M1-receptor antagonist) concentration-dependently increased the ACh release. The EC<SUB>50</SUB> values for these antagonists were 15 nM for atropine, 7.8 μM for pirenzepine, 0.39 μM for AF-DX116 and 59 nM for 4-DAMP, suggesting the autoregulation of the ACh release through an activation of M<SUB>2</SUB> and M<SUB>3</SUB> subtypes of muscarinic receptors in the SON. The postsynaptic effect of muscarinic receptors on urine outflow was studied by microinjection of selective muscarinic receptor agonists and antagonists into the SON. McN-A-343 (a M<SUB>1</SUB>-receptor agonist) had no significant effect on urine outflow. Pre-microinjection of atropine, 4-DAMP, <I>p</I>-F-HHSiD (a M<SUB>3</SUB>-receptor Antagonist) or pirenzepine into the SON concentration-dependently attenuated the oxotremorine-induced antidiuresis. In contrast, AF-DX116 and methoctramine had no effect on this oxotremorine-induced action. These results suggest that the M<SUB>3</SUB>-subtype may contribute to the antidiuretic actions. Nicotine produced an increase in ACh release in the SON and also induced potent antidiuretic effects, both of which were inhibited by hexamethonium. Thus, in the SON, the ACh release may be autoregulated by M<SUB>2</SUB>- and M<SUB>3</SUB>-subtypes of muscarinic receptors and the antidiuretic effects of ACh produced through an activation of the M<SUB>3</SUB>-subtype.
- 公益社団法人 日本薬理学会の論文
著者
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Tsushima Hiromi
Department Of Cellular And Molecular Pharmacology Nagoya City University Graduate School Of Medical
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Kamiya Toshio
Department Of Inorganic Materials Faculty Of Engineering Tokyo Institute Of Technology
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Matsuda Tomohiro
Department Of Epidemiology National Institute Of Public Health
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Mori Mayumi
Department Of Anesthesiology School Of Medicine Fukuoka University
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Kamiya Toshio
Department of Pharmacology, Nagoya City University Medical School, Kawasumi, Mizuho-ku, Nagoya 467, Japan
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Tsushima Hiromi
Department of Pharmacology, Nagoya City University Medical School, Kawasumi, Mizuho-ku, Nagoya 467, Japan
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