Desensitization of guinea-pig taenia caeci smooth muscle induced by a low concentration of carbachol. 2007

Shigeru Hishinuma, and Ryo Sato, and Masaki Saito
Department of Pharmacodynamics, Meiji Pharmaceutical University, Tokyo, Japan. hishi@my-pharm.ac.jp

1. In guinea-pig taenia caeci smooth muscle we have found that 10(-4) mol/L carbachol-induced desensitization to muscarinic agonists develops within 15-30 s, followed by transient resensitization at 1 min, whereas the desensitization to depolarizing high K(+) develops with maximal desensitization at 1 min followed by sustained resensitization up to 30 min. In both cases, Ca(2+)-dependent processes play a crucial role in determining the development of desensitization. 2. To elucidate whether these peculiar processes of desensitization/resensitization may be induced by a lower concentration of carbachol, we examined the development of desensitization induced by 10(-6) mol/L carbachol, because at this concentration carbachol is known to induce biphasic changes in intracellular Ca(2+) concentrations, with a smaller transient increase followed by a larger sustained increase than seen with 10(-4) mol/L carbachol. 3. Contractile responses to muscarinic agonists (carbachol or AHR-602) and high K(+) were desensitized by pretreatment with 10(-6) mol/L carbachol for 30 min in a manner dependent on the presence of extracellular Ca(2+). 4. The development of 10(-6) mol/L carbachol-induced desensitization to these muscarinic agonists in the presence of extracellular Ca(2+) showed three successive phases: fast desensitization within 30 s, followed by transient resensitization at 1 min and the subsequent development of desensitization up to 30 min. In contrast, desensitization to high K(+) did not develop up to 10 min and significant desensitization occurred at 30 min, with no apparent resensitization phase. 5. These results suggest that the characteristics of the Ca(2+)-dependent development of desensitization to muscarinic agonists, but not to high K(+), are well maintained in desensitization induced by a lower concentration of carbachol.

UI MeSH Term Description Entries
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002432 Cecum The blind sac or outpouching area of the LARGE INTESTINE that is below the entrance of the SMALL INTESTINE. It has a worm-like extension, the vermiform APPENDIX. Cecums
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea

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