Abstract
1. Microinjection of selective antibodies into superior cervical ganglion (SCG) neurones has identified the G-protein alpha-subunits mediating muscarinic receptor inhibition of M-type K+ current (IK(M)) and alpha-adrenoceptor inhibition of Ca2+ current (ICa). 2. Antibodies specific for G alpha q/11, but not those for G alpha o, reduced M-current inhibition by the muscarinic agonist oxotremorine-M, whereas anti-G alpha o antibodies, but not anti-G alpha q/11 or anti-G alpha i1-3 antibodies, reduced calcium current inhibition by noradrenaline. 3. Immunoblots with specific anti-G-protein antibodies demonstrated the presence of both G alpha q and G alpha 11, while G alpha o1 (but virtually no G alpha o2) was present. 4. We conclude that M1 muscarinic receptor inhibition of IK(M) is transduced by G alpha q and/or G alpha 11, and that G alpha o transduces alpha-adrenoceptor inhibition of ICa.
MeSH Terms
Adrenergic alpha-Agonists/pharmacology
Animals
Antibodies/immunology
Calcium/physiology
Calcium Channel Blockers/pharmacology
Electric Conductivity
GTP-Binding Proteins/immunology,physiology
Ganglia, Sympathetic/cytology,physiology
Neurons/physiology
Potassium Channel Blockers
Potassium Channels/classification,physiology
Rats
Receptors, Muscarinic/physiology
Chemicals
Adrenergic alpha-Agonists
Antibodies
Calcium Channel Blockers
Potassium Channel Blockers
Potassium Channels
Receptors, Muscarinic
GTP-Binding Proteins
Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Caulfield M P
Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London.
Jones S
Vallis Y
Buckley N J
Kim G D
Milligan G
Brown D A
References (18)
18 references, click to expand
-
Control of calcium current in rat sympathetic neurons by norepinephrine.
Brain Res. 1982 Jul 22;244(1):135-44
PMID: 6288175
-
On the mechanism of M-current inhibition by muscarinic m1 receptors in DNA-transfected rodent neuroblastoma x glioma cells.
J Physiol. 1993 Sep;469:153-78
PMID: 8271196
-
Antibodies directed against synthetic peptides distinguish between GTP-binding proteins in neutrophil and brain.
J Biol Chem. 1987 Oct 25;262(30):14683-8
PMID: 3117789
-
Muscarinic activation of ionic currents measured by a new whole-cell recording method.
J Gen Physiol. 1988 Aug;92(2):145-59
PMID: 2459299
-
Muscarinic suppression of the M-current in the rat sympathetic ganglion is mediated by receptors of the M1-subtype.
Br J Pharmacol. 1989 Oct;98(2):557-73
PMID: 2819334
-
On the transduction mechanism for muscarine-induced inhibition of M-current in cultured rat sympathetic neurones.
J Physiol. 1989 Jun;413:469-88
PMID: 2689633
-
Antibodies to the GTP binding protein, Go, antagonize noradrenaline-induced calcium current inhibition in NG108-15 hybrid cells.
Neuron. 1989 Aug;3(2):177-82
PMID: 2560391
-
Identification of two distinct isoforms of the guanine nucleotide binding protein G0 in neuroblastoma X glioma hybrid cells: independent regulation during cyclic AMP-induced differentiation.
J Neurochem. 1990 Dec;55(6):1890-8
PMID: 2172464
-
Diversity of G proteins in signal transduction.
Science. 1991 May 10;252(5007):802-8
PMID: 1902986
-
A diffusible second messenger mediates one of the pathways coupling receptors to calcium channels in rat sympathetic neurons.
Neuron. 1991 Jun;6(6):859-67
PMID: 1647174
-
Widespread distribution of Gq alpha/G11 alpha detected immunologically by an antipeptide antiserum directed against the predicted C-terminal decapeptide.
FEBS Lett. 1991 Aug 5;287(1-2):171-4
PMID: 1908788
-
Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents.
Nature. 1991 Sep 5;353(6339):43-8
PMID: 1679199
-
Molecular interaction of the human alpha 2-C10-adrenergic receptor, when expressed in Rat-1 fibroblasts, with multiple pertussis toxin-sensitive guanine nucleotide-binding proteins: studies with site-directed antisera.
Mol Pharmacol. 1991 Nov;40(5):627-32
PMID: 1658601
-
Pertussis toxin and voltage dependence distinguish multiple pathways modulating calcium channels of rat sympathetic neurons.
Neuron. 1992 Jan;8(1):97-106
PMID: 1346090
-
Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11, and phospholipase C-beta 1.
J Biol Chem. 1992 Apr 25;267(12):8081-8
PMID: 1341877
-
Closure of potassium M-channels by muscarinic acetylcholine-receptor stimulants requires a diffusible messenger.
Proc Biol Sci. 1992 Nov 23;250(1328):119-25
PMID: 1361985
-
The human muscarinic M1 acetylcholine receptor, when express in CHO cells, activates and downregulates both Gq alpha and G11 alpha equally and non-selectively.
FEBS Lett. 1993 Jun 14;324(2):241-5
PMID: 8508928
-
Rapid accumulation of inositol phosphates in isolated rat superior cervical sympathetic ganglia exposed to V1-vasopressin and muscarinic cholinergic stimuli.
Biochem J. 1984 Aug 1;221(3):803-11
PMID: 6148075