title: Role of various kinases in muscarinic M3 receptor-mediated contraction of longitudinal muscle of rat colon.
abstract: The longitudinal muscle layer in gut is the functional opponent to the circular muscle layer during peristalsis. Differences in innervation of the layers allow for the contraction of one layer concurrently with the relaxation of the other, enabling the passage of gut contents in a controlled fashion. Differences in development have given the cells of the two layers differences in receptor populations, membrane lipid handling, and calcium handling profiles/behaviors. The contractile activity of the longitudinal muscle is largely mediated by cholinergic neural input from myenteric plexus. Activation of muscarinic receptors leads to rapid activation of several kinases including MLC kinase, ERK1/2, CaMKII and Rho kinase. Phosphorylation of myosin light chain (MLC20) by MLC kinase (MLCK) is a prerequisite for contraction in both circular and longitudinal muscle cells. In rat colonic longitudinal muscle strips, we measured muscarinic receptor-mediated contraction following incubation with kinase inhibitors. Basal tension was differentially regulated by Rho kinase, ERK1/2, CaMKII and CaMKK. Selective inhibitors of Rho kinase, ERK1/2, CaMKK/AMPK, and CaMKII each reduced carbachol-induced contraction in the innervated muscle strips. These inhibitors had no direct effect on MLCK activity. Thus unlike previously reported for isolated muscle cells where CaMKII and ERK1/2 are not involved in contraction, we conclude that the regulation of carbachol-induced contraction in innervated longitudinal muscle strips involves the interplay of Rho kinase, ERK1/2, CaMKK/AMPK, and CAMKII.
authors.affiliation: Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Anderson
authors.forename: Derek M
authors.initials: DM
authors.lastname: Kendig
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Qudah
authors.forename: Sunila
authors.initials: S
authors.lastname: Mahavadi
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
authors.forename: John R
authors.initials: JR
authors.lastname: Grider
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000502:physiology; D003106:Colon / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D009197:Myenteric Plexus / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000502:physiology*; D053644:Naphthalimides / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000577:Amides; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D053644:Naphthalimides; D010446:Peptide Fragments; D011725:Pyridines; D043587:Receptor, Muscarinic M3; C090954:SM 1 peptide; C458525:STO 609; C108830:Y 27632; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002217:Carbachol; D054460:rho-Associated Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D009219:Myosin-Light-Chain Kinase; D048052:Mitogen-Activated Protein Kinase 3