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Beta gamma subunits of GTP-binding proteins inhibit muscarinic receptor stimulation of phospholipase C.
Moriarty TM
,
Gillo B
,
Carty DJ
,
Premont RT
,
Landau EM
,
Iyengar R
.
Abstract
This study examines the mechanism of guanine nucleotide-binding protein (G protein) coupling of receptors to phospholipase C. The Xenopus oocyte has a muscarinic receptor-activated Cl- current that is mediated by inositol 1,4,5-trisphosphate. Modulation of the muscarinic receptor-evoked Cl- current was examined under voltage clamp in oocytes injected with resolved G-protein subunits. The presence of an alpha subunit of G proteins in oocytes was shown by pertussis toxin-labeling of a 41-kDa band in oocyte membranes. The presence of the beta subunit of G proteins was demonstrated by immunoblotting experiments with an antiserum (U-49) that is specific for the beta subunit. Pertussis toxin treatment of oocytes resulted in the uncoupling of muscarinic receptors from activation of the Cl- current. Cells microinjected with 1.5 ng of human erythrocyte beta gamma-subunit complex or 1.0 ng of bovine brain beta gamma-subunit complex showed approximately a 95% reduction in the evoked Cl- current. Cells injected with equal volumes of protein storage vehicle showed no change in response. Cells injected with boiled beta gamma subunits, bovine serum albumin, or resolved alpha subunits also showed no reduction in response. Cells injected with various concentrations of beta gamma subunits showed a concentration dependence with half-maximal inhibition of the muscarinic activated Cl- current at about 10 nM. Cells injected with 1.0 ng of bovine brain beta gamma subunits could not respond to bath-applied agonist but could generate the Cl- current on intracellular injection of inositol 1,4,5-trisphosphate. These observations suggest that there is a G protein responsible for muscarinic receptor-mediated signal transduction through phospholipase C and that it is an alpha beta gamma heterotrimer. It appears that the mode of action of the G protein in the phospholipase C system may be similar to that of the hormone-activated adenylyl cyclase.
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983, Pubmed,
Xenbase
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase
Beckner,
The ras oncogene product p21 is not a regulatory component of adenylate cyclase.
,
Pubmed
Berridge,
Inositol trisphosphate and diacylglycerol: two interacting second messengers.
1987,
Pubmed
Burch,
Phospholipase A2 and phospholipase C are activated by distinct GTP-binding proteins in response to alpha 1-adrenergic stimulation in FRTL5 thyroid cells.
1986,
Pubmed
Casey,
G protein involvement in receptor-effector coupling.
1988,
Pubmed
Cassel,
Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system.
1978,
Pubmed
Cerione,
Functional differences in the beta gamma complexes of transducin and the inhibitory guanine nucleotide regulatory protein.
1987,
Pubmed
Cockcroft,
Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase.
,
Pubmed
Codina,
Ns and Ni, the stimulatory and inhibitory regulatory components of adenylyl cyclases. Purification of the human erythrocyte proteins without the use of activating regulatory ligands.
1984,
Pubmed
Codina,
The alpha subunit of the GTP binding protein Gk opens atrial potassium channels.
1987,
Pubmed
Dascal,
Types of muscarinic response in Xenopus oocytes.
1980,
Pubmed
,
Xenbase
Dascal,
Xenopus oocyte resting potential, muscarinic responses and the role of calcium and guanosine 3',5'-cyclic monophosphate.
1984,
Pubmed
,
Xenbase
Dascal,
The use of Xenopus oocytes for the study of ion channels.
1987,
Pubmed
,
Xenbase
Gillo,
The involvement of inositol 1,4,5-trisphosphate and calcium in the two-component response to acetylcholine in Xenopus oocytes.
1987,
Pubmed
,
Xenbase
Gilman,
G proteins: transducers of receptor-generated signals.
1987,
Pubmed
Hescheler,
Angiotensin II-induced stimulation of voltage-dependent Ca2+ currents in an adrenal cortical cell line.
1988,
Pubmed
Hescheler,
The GTP-binding protein, Go, regulates neuronal calcium channels.
,
Pubmed
Iyengar,
Identification of a new GTP-binding protein. A Mr = 43,000 substrate for pertussis toxin.
1987,
Pubmed
Jelsema,
Light activation of phospholipase A2 in rod outer segments of bovine retina and its modulation by GTP-binding proteins.
1987,
Pubmed
Kobilka,
Functional activity and regulation of human beta 2-adrenergic receptors expressed in Xenopus oocytes.
1987,
Pubmed
,
Xenbase
Kojima,
Pertussis toxin blocks angiotensin II-induced calcium influx but not inositol trisphosphate production in adrenal glomerulosa cell.
1986,
Pubmed
Kusano,
Acetylcholine receptors in the oocyte membrane.
,
Pubmed
,
Xenbase
Laemmli,
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
1970,
Pubmed
Logothetis,
The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart.
,
Pubmed
Mumby,
Antisera of designed specificity for subunits of guanine nucleotide-binding regulatory proteins.
1986,
Pubmed
Olate,
Oocyte adenylyl cyclase contains Ni, yet the guanine nucleotide-dependent inhibition by progesterone is not sensitive to pertussis toxin.
1984,
Pubmed
,
Xenbase
Oron,
Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes.
,
Pubmed
,
Xenbase
Pfaffinger,
GTP-binding proteins couple cardiac muscarinic receptors to a K channel.
,
Pubmed
