Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 30 October 1987:
Vol. 238. no. 4827, pp. 672 - 675
DOI: 10.1126/science.2823384

Articles

Science, Vol 238, Issue 4827, 672-675
Copyright © 1987 by American Association for the Advancement of Science


articles

An M2 muscarinic receptor subtype coupled to both adenylyl cyclase and phosphoinositide turnover

A Ashkenazi, JW Winslow, EG Peralta, GL Peterson, MI Schimerlik, DJ Capon, and J Ramachandran

Department of Developmental Biology, Genentech, Inc., South San Francisco, CA 94080.

To investigate whether a particular receptor subtype can be coupled to multiple effector systems, recombinant M2 muscarinic receptors were expressed in cells lacking endogenous receptor. The muscarinic agonist carbachol both inhibited adenylyl cyclase and stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was significantly less efficient and more dependent on receptor levels than the inhibition of adenylyl cyclase. Both responses were mediated by guanine nucleotide binding proteins, as evidenced by their inhibition by pertussis toxin; the more efficiently coupled adenylyl cyclase response was significantly more sensitive. Thus, individual subtypes of a given receptor are capable of regulating multiple effector pathways.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
M2 Muscarinic Receptors Induce Airway Smooth Muscle Activation via a Dual, G{beta}{gamma}-mediated Inhibition of Large Conductance Ca2+-activated K+ Channel Activity.
X.-B. Zhou, I. Wulfsen, S. Lutz, E. Utku, U. Sausbier, P. Ruth, T. Wieland, and M. Korth (2008)
J. Biol. Chem. 283, 21036-21044
   Abstract »    Full Text »    PDF »
M1 and M3 Muscarinic Receptors Control Physiological Processing of Cellular Prion by Modulating ADAM17 Phosphorylation and Activity.
M. Alfa Cisse, C. Sunyach, B. E. Slack, A. Fisher, B. Vincent, and F. Checler (2007)
J. Neurosci. 27, 4083-4092
   Abstract »    Full Text »    PDF »
Muscarinic M2 Receptors Directly Activate Gq/11 and Gs G-Proteins.
P. Michal, E. E. El-Fakahany, and V. Dolezal (2007)
J. Pharmacol. Exp. Ther. 320, 607-614
   Abstract »    Full Text »    PDF »
Differential Coupling of Muscarinic M1, M2, and M3 Receptors to Phosphoinositide Hydrolysis in Urinary Bladder and Longitudinal Muscle of the Ileum of the Mouse.
J. A. Tran, M. Matsui, and F. J. Ehlert (2006)
J. Pharmacol. Exp. Ther. 318, 649-656
   Abstract »    Full Text »    PDF »
Cholinergic agonists transactivate EGFR and stimulate MAPK to induce goblet cell secretion.
H. Kanno, Y. Horikawa, R. R. Hodges, D. Zoukhri, M. A. Shatos, J. D. Rios, and D. A. Dartt (2003)
Am J Physiol Cell Physiol 284, C988-C998
   Abstract »    Full Text »    PDF »
Mechanisms and Physiological Significance of the Cholinergic Control of Pancreatic {beta}-Cell Function.
P. Gilon and J.-C. Henquin (2001)
Endocr. Rev. 22, 565-604
   Abstract »    Full Text »    PDF »
delta -Opioid Receptors Are More Efficiently Coupled to Adenylyl Cyclase Than to L-Type Ca2+ Channels in Transfected Rat Pituitary Cells.
P. L. Prather, L. Song, E. T. Piros, P. Y. Law, and T. G. Hales (2000)
J. Pharmacol. Exp. Ther. 295, 552-562
   Abstract »    Full Text »
A multiplicity of muscarinic mechanisms: Enough signaling pathways to take your breath away.
N. M. Nathanson (2000)
PNAS 97, 6245-6247
   Full Text »    PDF »
The G Protein alpha Subunit Has a Key Role in Determining the Specificity of Coupling to, but Not the Activation of, G Protein-gated Inwardly Rectifying K+ Channels.
J. L. Leaney, G. Milligan, and A. Tinker (2000)
J. Biol. Chem. 275, 921-929
   Abstract »    Full Text »    PDF »
A low resolution model for the interaction of G proteins with G protein-coupled receptors.
L. Oliveira, A.C.M. Paiva, and G. Vriend (1999)
Protein Eng. Des. Sel. 12, 1087-1095
   Abstract »    Full Text »    PDF »
Biphasic, Opposing Modulation of Cloned Neuronal alpha 1E Ca Channels by Distinct Signaling Pathways Coupled to M2 Muscarinic Acetylcholine Receptors.
U. Meza, R. Bannister, K. Melliti, and B. Adams (1999)
J. Neurosci. 19, 6806-6817
   Abstract »    Full Text »    PDF »
Regulation of cardiac {beta}-adrenergic response by nitric oxide.
J.-L. Balligand (1999)
Cardiovasc Res 43, 607-620
   Full Text »    PDF »
Differential inflammatory modulation of canine ileal longitudinal and circular muscle cells.
X.-Z. Shi and S. K. Sarna (1999)
Am J Physiol Gastrointest Liver Physiol 277, G341-G350
   Abstract »    Full Text »    PDF »
Muscarinic M3 Receptor Inactivation Reveals a Pertussis Toxin-Sensitive Contractile Response in the Guinea Pig Colon: Evidence for M2/M3 Receptor Interactions.
G. W. Sawyer and F. J. Ehlert (1999)
J. Pharmacol. Exp. Ther. 289, 464-476
   Abstract »    Full Text »
Gonadotropin-Releasing Hormone Receptor Couples to Multiple G Proteins in Rat Gonadotrophs and in GGH3 Cells: Evidence from Palmitoylation and Overexpression of G proteins.
D. Stanislaus, S. Ponder, T. H. Ji, and P. M. Conn (1998)
Biol Reprod 59, 579-586
   Abstract »    Full Text »
International Union of Pharmacology. XVII. Classification of Muscarinic Acetylcholine Receptors.
M. P. Caulfield and N. J. M. Birdsall (1998)
Pharmacol. Rev. 50, 279-290
   Abstract »    Full Text »    PDF »
Pharmacological Comparison of the Cloned Human and Rat M2 Muscarinic Receptor Genes Expressed in the Murine Fibroblast (B82) Cell Line.
I. Kovacs, H. I. Yamamura, S. L. Waite, E. V. Varga, and W. R. Roeske (1998)
J. Pharmacol. Exp. Ther. 284, 500-507
   Abstract »    Full Text »
The N-terminal Extension of Galpha q Is Critical for Constraining the Selectivity of Receptor Coupling.
E. Kostenis, M. Y. Degtyarev, B. R. Conklin, and J. Wess (1997)
J. Biol. Chem. 272, 19107-19110
   Abstract »    Full Text »    PDF »
Both Overlapping and Distinct Signaling Pathways for Somatostatin Receptor Subtypes SSTR1 and SSTR2 in Pituitary Cells.
L. Chen, V. D. Fitzpatrick, R. L. Vandlen, and A. H. Tashjian Jr. (1997)
J. Biol. Chem. 272, 18666-18672
   Abstract »    Full Text »    PDF »
Adenosine A1 Receptor-Mediated Activation of Phospholipase C in Cultured Astrocytes Depends on the Level of Receptor Expression.
K. Biber, K.-N. Klotz, M. Berger, P. J. Gebicke-Harter, and D. van Calker (1997)
J. Neurosci. 17, 4956-4964
   Abstract »    Full Text »    PDF »
Effect of Gastrin-Releasing Peptide Receptor Number on Receptor Affinity, Coupling, Degradation, and Modulation.
T. Tsuda, T. Kusui, W. Hou, R. V. Benya, M. A. Akeson, G. S. Kroog, J. F. Battey, and R. T. Jensen (1997)
Mol. Pharmacol. 51, 721-732
   Abstract »    Full Text »
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.
E. C. Kohn, R. Alessandro, J. Probst, W. Jacobs, E. Brilley, and C. C. Felder (1996)
J. Biol. Chem. 271, 17476-17484
   Abstract »    Full Text »    PDF »
Physiological and Biochemical Evidence for Coordinate Increases in Muscarinic Receptors and Gi During Pacing-Induced Heart Failure.
D. E. Vatner, N. Sato, J. B. Galper, and S. F. Vatner (1996)
Circulation 94, 102-107
   Abstract »    Full Text »
Desensitization and Internalization of the m2 Muscarinic Acetylcholine Receptor Are Directed by Independent Mechanisms.
R. Pals-Rylaarsdam, Y. Xu, P. Witt-Enderby, J. L. Benovic, and M. M. Hosey (1995)
J. Biol. Chem. 270, 29004-29011
   Abstract »    Full Text »    PDF »
Porcine m2 Muscarinic Acetylcholine Receptor-Effector Coupling in Chinese Hamster Ovary Cells.
W. K. Vogel, V. A. Mosser, D. A. Bulseco, and M. I. Schimerlik (1995)
J. Biol. Chem. 270, 15485-15493
   Abstract »    Full Text »    PDF »
M[IMAGE]Muscarinic Receptors Heterologously Expressed in Cardiac Myocytes Mediate Ras-dependent Changes in Gene Expression.
M. T. Ramirez, G. R. Post, P. V. Sulakhe, and J. H. Brown (1995)
J. Biol. Chem. 270, 8446-8451
   Abstract »    Full Text »    PDF »
Tyrosine Phosphorylation-dependent Stimulation of Amyloid Precursor Protein Secretion by the m3 Muscarinic Acetylcholine Receptor.
B. E. Slack, J. Breu, M. A. Petryniak, K. Srivastava, and R. J. Wurtman (1995)
J. Biol. Chem. 270, 8337-8344
   Abstract »    Full Text »    PDF »
Transcriptional Down-regulation of m2 Muscarinic Receptor Gene Expression in Human Embryonic Lung (HEL 299) Cells by Protein Kinase C.
J. Rousell, E.-B. Haddad, J. C. W. Mak, and P. J. Barnes (1995)
J. Biol. Chem. 270, 7213-7218
   Abstract »    Full Text »    PDF »
Impaired Endothelium-Dependent Vasodilation in Patients With Essential Hypertension : Evidence That Nitric Oxide Abnormality Is Not Localized to a Single Signal Transduction Pathway.
J. A. Panza, C. E. Garcia, C. M. Kilcoyne, A. A. Quyyumi, and R. O. Cannon III (1995)
Circulation 91, 1732-1738
   Abstract »    Full Text »
Functional Analysis of a Dominant Negative Mutant of Galpha[IMAGE].
V. Z. Slepak, A. Katz, and M. I. Simon (1995)
J. Biol. Chem. 270, 4037-4041
   Abstract »    Full Text »    PDF »
Cell cycle-dependent coupling of the calcitonin receptor to different G proteins.
M Chakraborty, D Chatterjee, S Kellokumpu, H Rasmussen, and R Baron (1991)
Science 251, 1078-1082
   Abstract »    PDF »
Heterologous expression of excitability proteins: route to more specific drugs?.
H. Lester (1988)
Science 241, 1057-1063
   Abstract »    PDF »
Fertilization events induced by neurotransmitters after injection of mRNA in Xenopus eggs.
D Kline, L Simoncini, G Mandel, R. Maue, R. Kado, and L. Jaffe (1988)
Science 241, 464-467
   Abstract »    PDF »
Muscarinic Acetylcholine Receptors Induce the Expression of the Immediate Early Growth Regulatory Gene CYR61.
C. Albrecht, H. von der Kammer, M. Mayhaus, J. Klaudiny, M. Schweizer, and R. M. Nitsch (2000)
J. Biol. Chem. 275, 28929-28936
   Abstract »    Full Text »    PDF »
Overexpression of beta 1 and beta 2 Adrenergic Receptors in Rat Atrial Myocytes. DIFFERENTIAL COUPLING TO G PROTEIN-GATED INWARD RECTIFIER K+ CHANNELS VIA Gs AND Gi/o.
M.-C. Wellner-Kienitz, K. Bender, and L. Pott (2001)
J. Biol. Chem. 276, 37347-37354
   Abstract »    Full Text »    PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)