Characterization of muscarinic receptor-mediated cationic currents in longitudinal smooth muscle cells of mouse small intestine
Autor: | Mai Uchiyama, Seiichi Komori, Takashi Sakamoto, Masakazu Nishimura, Hayato Matsuyama, Toshihiro Unno, Mitsunobu Hattori |
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Rok vydání: | 2006 |
Předmět: |
Agonist
Male medicine.medical_specialty Carbachol medicine.drug_class Guinea Pigs Myocytes Smooth Muscle Gating Muscarinic Antagonists Biology Cholinergic Agonists Diamines In Vitro Techniques Pertussis toxin Ion Channels Membrane Potentials Mice Piperidines Internal medicine Cations Muscarinic acetylcholine receptor Intestine Small medicine Myocyte Animals Enzyme Inhibitors Estrenes Pharmacology Membrane potential Receptor Muscarinic M3 Receptor Muscarinic M2 Phospholipase C Dose-Response Relationship Drug lcsh:RM1-950 Pyrrolidinones Endocrinology lcsh:Therapeutics. Pharmacology Pertussis Toxin Type C Phospholipases Biophysics Molecular Medicine Ion Channel Gating medicine.drug |
Zdroj: | Journal of Pharmacological Sciences, Vol 100, Iss 3, Pp 215-226 (2006) |
ISSN: | 1347-8613 |
Popis: | In mouse intestinal smooth muscle cells held at −50 mV, carbachol evoked an atropine-sensitive inward current in the intracellular presence of Cs+. The current response consisted of an initial peak followed by a smaller plateau component on which oscillatory currents frequently arose. Results from various experimental procedures indicated that the inward current is a muscarinic receptor-operated cationic current (mIcat) sensitive to cytosolic Ca2+ concentration ([Ca2+]i) and that the initial peak and oscillatory components are contaminated by Ca2+-activated Cl− currents. Under conditions of [Ca2+]i buffered to 100 nM, the mIcat response to cumulative carbachol applications was inhibited competitively by an M2-selective antagonist but non-competitively by an M3-selective one. Also it was severely reduced by pertussis toxin (PTX) treatment or a phospholipase C (PLC) inhibitor. Comparative analysis of mIcat in mouse and guinea-pig intestinal myocytes indicated that the underlying channels resemble between those myocytes in agonist sensitivity, current-voltage relationship, and unitary conductance. The results suggest that in mouse intestinal myocytes, mIcat arises mainly via an M2/M3 synergistic mechanism involving PTX-sensitive G-proteins and PLC activity in the absence of current modulation by [Ca2+]i changes, as described for guinea-pig ileal mIcat. The channels underlying mIcat are also indistinguishable in gating properties between both types of myocytes. Keywords:: muscarinic receptor, receptor-oparated cation channel, purtussis toxin, phospholipase C, intestinal smooth muscle |
Databáze: | OpenAIRE |
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