HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Felder, C. C. Articles by Axelrod, J. Search for Related Content PubMed PubMed Citation Articles by Felder, C. C. Articles by Axelrod, J. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 264, Issue 34, 20356-20362, Dec, 1989

A transfected m1 muscarinic acetylcholine receptor stimulates adenylate cyclase via phosphatidylinositol hydrolysis

CC Felder, RY Kanterman, AL Ma and J Axelrod
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892.

The m1 muscarinic acetylcholine receptor gene was transfected into and stably expressed in A9 L cells. The muscarinic receptor agonist, carbachol, stimulated inositol phosphate generation, arachidonic acid release, and cAMP accumulation in these cells. Carbachol stimulated arachidonic acid and inositol phosphate release with similar potencies, while cAMP generation required a higher concentration. Studies were performed to determine if the carbachol-stimulated cAMP accumulation was due to direct coupling of the m1 muscarinic receptor to adenylate cyclase via a GTP binding protein or mediated by other second messengers. Carbachol failed to stimulate adenylate cyclase activity in A9 L cell membranes, whereas prostaglandin E2 did, suggesting indirect stimulation. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), stimulated arachidonic acid release yet inhibited cAMP accumulation in response to carbachol. PMA also inhibited inositol phosphate release in response to carbachol, suggesting that activation of phospholipase C might be involved in cAMP accumulation. PMA did not inhibit prostaglandin E2-, cholera toxin-, or forskolin-stimulated cAMP accumulation. The phospholipase A2 inhibitor eicosatetraenoic acid and the cyclooxygenase inhibitors indomethacin and naproxen had no effect on carbachol-stimulated cAMP accumulation. Carbachol-stimulated cAMP accumulation was inhibited with TMB-8, an inhibitor of intracellular calcium release, and W7, a calmodulin antagonist. These observations suggest that carbachol-stimulated cAMP accumulation does not occur through direct m1 muscarinic receptor coupling or through the release of arachidonic acid and its metabolites, but is mediated through the activation of phospholipase C. The generation of cytosolic calcium via inositol 1,4,5-trisphosphate and subsequent activation of calmodulin by m1 muscarinic receptor stimulation of phospholipase C appears to generate the accumulation of cAMP.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. L. Thomas, R. Mistry, C. J. Langmead, M. D. Wood, and R. A. J. Challiss G Protein Coupling and Signaling Pathway Activation by M1 Muscarinic Acetylcholine Receptor Orthosteric and Allosteric Agonists J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 365 - 374. [Abstract] [Full Text] [PDF]

				P. Michal, E. E. El-Fakahany, and V. Dolezal Muscarinic M2 Receptors Directly Activate Gq/11 and Gs G-Proteins J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 607 - 614. [Abstract] [Full Text] [PDF]

				B. Wenzel, N. Elsner, and R. Heinrich mAChRs in the Grasshopper Brain Mediate Excitation by Activation of the AC/PKA and the PLC Second-Messenger Pathways J Neurophysiol, February 1, 2002; 87(2): 876 - 888. [Abstract] [Full Text] [PDF]

				R. Heinrich, B. Wenzel, and N. Elsner A role for muscarinic excitation: Control of specific singing behavior by activation of the adenylate cyclase pathway in the brain of grasshoppers PNAS, June 28, 2001; (2001) 151131998. [Abstract] [Full Text] [PDF]

				A Llorente, B van Deurs, O Garred, P Eker, and K Sandvig Apical endocytosis of ricin in MDCK cells is regulated by the cyclooxygenase pathway J. Cell Sci., January 4, 2000; 113(7): 1213 - 1221. [Abstract] [PDF]

				P. Onali and M. C. Olianas Identification and Characterization of Muscarinic Receptors Potentiating the Stimulation of Adenylyl Cyclase Activity by Corticotropin-Releasing Hormone in Membranes of Rat Frontal Cortex J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 753 - 759. [Abstract] [Full Text]

				M. Garnier, M. Lamacz, L. Galas, S. Lenglet, M.-C. Tonon, and H. Vaudry Pharmacological and Functional Characterization of Muscarinic Receptors in the Frog Pars Intermedia Endocrinology, August 1, 1998; 139(8): 3525 - 3533. [Abstract] [Full Text] [PDF]

				H. von der Kammer, M. Mayhaus, C. Albrecht, J. Enderich, M. Wegner, and R. M. Nitsch Muscarinic Acetylcholine Receptors Activate Expression of the Egr Gene Family of Transcription Factors J. Biol. Chem., June 5, 1998; 273(23): 14538 - 14544. [Abstract] [Full Text] [PDF]

				M.-Y. Chen, Y. Long, and P. N. Devreotes A novel cytosolic regulator, Pianissimo, is required for chemoattractant receptor and G protein-mediated activation of the 12 transmembrane domain adenylyl cyclase in Dictyostelium Genes & Dev., December 1, 1997; 11(23): 3218 - 3231. [Abstract] [Full Text] [PDF]

				J. Del Valle and I. Gantz Novel insights into histamine H2 receptor biology Am J Physiol Gastrointest Liver Physiol, November 1, 1997; 273(5): G987 - G996. [Abstract] [Full Text] [PDF]

				K. S. Murthy and G. M. Makhlouf Differential Coupling of Muscarinic m2 and m3 Receptors to Adenylyl Cyclases V/VI in Smooth Muscle. CONCURRENT m2-MEDIATED INHIBITION VIA Galpha i3 AND m3-MEDIATED STIMULATION VIA Gbeta gamma q J. Biol. Chem., August 22, 1997; 272(34): 21317 - 21324. [Abstract] [Full Text] [PDF]

				C. C. Gerhardt, R. A. Bakker, G. J. Piek, R. J. Planta, E. Vreugdenhil, J. E. Leysen, and H. Van Heerikhuizen Molecular Cloning and Pharmacological Characterization of a Molluscan Octopamine Receptor Mol. Pharmacol., February 1, 1997; 51(2): 293 - 300. [Abstract] [Full Text] [PDF]

				TrevorJ. Shuttleworth and T. J. Shuttleworth Arachidonic Acid Activates the Noncapacitative Entry of Ca2+ during [Ca2+]i Oscillations J. Biol. Chem., September 6, 1996; 271(36): 21720 - 21725. [Abstract] [Full Text] [PDF]

				A. Horstmeyer, H. Cramer, T. Sauer, W. Muller-Esterl, and C. Schroeder Palmitoylation of Endothelin Receptor A. DIFFERENTIAL MODULATION OF SIGNAL TRANSDUCTION ACTIVITY BY POST-TRANSLATIONAL MODIFICATION J. Biol. Chem., August 23, 1996; 271(34): 20811 - 20819. [Abstract] [Full Text] [PDF]

				E. C. Kohn, R. Alessandro, J. Probst, W. Jacobs, E. Brilley, and C. C. Felder Identification and Molecular Characterization of a m5 Muscarinic Receptor in A2058 Human Melanoma Cells. COUPLING TO INHIBITION OF ADENYLYL CYCLASE AND STIMULATION OF PHOSPHOLIPASE A2 J. Biol. Chem., July 19, 1996; 271(29): 17476 - 17484. [Abstract] [Full Text] [PDF]

				F. Nakamura, M. Kato, K. Kameyama, T. Nukada, T. Haga, H. Kato, T. Takenawa, and U. Kikkawa Characterization of G(q) Family G Proteins G[IMAGE]alpha (G(14)alpha), G[IMAGE]alpha (G[IMAGE]alpha), and G(q)alpha Expressed in the Baculovirus-Insect Cell System J. Biol. Chem., March 17, 1995; 270(11): 6246 - 6253. [Abstract] [Full Text] [PDF]

				C. Albrecht, H. von der Kammer, M. Mayhaus, J. Klaudiny, M. Schweizer, and R. M. Nitsch Muscarinic Acetylcholine Receptors Induce the Expression of the Immediate Early Growth Regulatory Gene CYR61 J. Biol. Chem., September 8, 2000; 275(37): 28929 - 28936. [Abstract] [Full Text] [PDF]

				R. Heinrich, B. Wenzel, and N. Elsner A role for muscarinic excitation: Control of specific singing behavior by activation of the adenylate cyclase pathway in the brain of grasshoppers PNAS, August 14, 2001; 98(17): 9919 - 9923. [Abstract] [Full Text] [PDF]