A physiological requirement of Na+ for the regulation of cAMP levels in intact NG108-15 cells

Lichtshtein, David; Boone, Gloria; Blume, Arthur J.

doi:10.1016/0024-3205(79)90504-6

Cited by 32 publications

(9 citation statements)

References 13 publications

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“…46 reported that 20-40 mM Na + (or Li + ) must be present in the extracellular medium for the observation of enkephalin regulation of intracellular cyclic AMP concentration in NG108-15 cells. 58 In contrast, muscarinic stimulation of GTPase and reciprocal inhibition of adenylate cyclase activities in canine cardiac sarcolemma was similar, whether in the presence of 150 mM Na + or in the presence of sodium-free concentrations far below the K^ for previously reported facilitative effects of the monovalent cation in other systems.…”

Section: Discussionmentioning

confidence: 74%

Muscarinic cholinergic-receptor stimulation of specific GTP hydrolysis related to adenylate cyclase activity in canine cardiac sarcolemma.

Fleming

Watanabe

1988

Circulation Research

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One component of muscarinic receptor inhibition of the function of cardiac ventricles is mediated by the inhibition of activated adenylate cyclase activity in sarcolemma. We have shown previously that muscarinic agonists inhibit GTP-but not Gpp(NH)p-activated adenylate cyclase activity, and various studies in other tissues indicate that nonhydrolyzable GTP analogues prevent inactivation of the enzyme. These data have suggested a role for GTP hydrolysis in the mechanism of inhibition of adenylate cyclase. The present study demonstrates that purified canine cardiac sarcolemma displays high-affinity GTPase activity that is reciprocally related to adenylate cyclase activity. The high-affinity GTPase activity was stimulated by muscarinic agonists and blocked by atropine. Furthermore, the one-half maximal effects of oxotremorine for binding to muscarinic receptors, stimulation of high-affinity GTPase activity, and inhibition of adenylate cyclase activity were similar. Muscarinic stimulation of GTPase activity and inhibition of adenylate cyclase activity required functional activity of the pertussis toxin (IAP) substrates). Treatment of sarcolemmal membranes with LAP attenuated the ability of oxotremorine to both stimulate high-affinity GTPase activity and inhibit adenylate cyclase activity. These studies indicate that muscarinic receptor stimulation of high-affinity GTPase activity dependent on functional LAP substrate(s) is closely linked to the mechanism of muscarinic inhibition of adenylate cyclase activity. (Circulation Research L988;64:340-350)

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Section: Discussionmentioning

confidence: 74%

Muscarinic cholinergic-receptor stimulation of specific GTP hydrolysis related to adenylate cyclase activity in canine cardiac sarcolemma.

Fleming

Watanabe

1988

Circulation Research

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“…tenuation of cAMP accumulation in intact cells and inhibition of adenylate cyclase activity in cell-free preparations (1)(2)(3)(4)(5)(6). The GTP dependence of this inhibition (4,5), the negative heterotropic effects of guanine nucleotides on agonist binding to inhibitory receptors (6)(7)(8), and knowledge of the role of the stimulatory guanine nucleotide regulatory protein (N,) in the mechanism of activation of adenylate cyclase (9) have led to the proposal that an inhibitory guanine nucleotide regulatory protein (N,) is involved in the mechanism of receptor-mediated inhibition of adenylate cyclase (10).…”

Section: Activation Of Muscarinic Cholinergic Receptors Results In At-mentioning

confidence: 99%

Pertussis toxin differentiates between two mechanisms of attenuation of cyclic AMP accumulation by muscarinic cholinergic receptors.

Hughes¹,

Martin²,

Harden³

1984

Proc. Natl. Acad. Sci. U.S.A.

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It has been proposed elsewhere [Meeker, R. B. & Harden, T. K. (1982) Mol. Pharmacol. 22, [310][311][312][313][314][315][316][317][318][319] that muscarinic cholinergic receptor-mediated attenuation of cAMP accumulation occurs through activation of phosphodiesterase in 1321N1 human astrocytoma cells. Pertussis toxin, which ADP-ribosylates the guanine nucleotide regulatory protein involved in receptor-mediated inhibition of adenylate cyclase (N1), has been utilized to further differentiate between the mechanism of cholinergic regulation of cAMP metabolism in 1321N1 cells and the mechanism involving inhibition of adenylate cyclase in other tissues. Muscarinic receptor-mediated regulation of cAMP accumulation in NG108-15 neuroblastoma-glioma cells occurs through inhibition of adenylate cyclase. Pretreatment of these cells with pertussis toxin completely blocked the capacity of carbachol to attenuate cAMP accumulation. In contrast, concentrations of pertussis toxin two to three orders of magnitude higher than those effective in NG108-15 cells had no effect on muscarinic receptor-mediated attentuation of cAMP accumulation in 1321N1 cells. In addition, no effect of pertussis toxin was observed either on the control rate or the carbachol-stimulated rate of cAMP degradation measured directly in intact 1321N1 cells. A 41,000 Mr protein previously proposed to be the a subunit of N. was labeled during incubation of a plasma membrane fraction from 1321N1 cells with [32P]NAD and pertussis toxin. Pertussis toxin is apparently active in 1321N1 cells, since this protein substrate was not labeled in plasma membrane preparations from cells previously incubated with toxin. Functional activity of N. was demonstrated by the observation that guanosine 5'-[y thioltriphosphate-and GTP-mediated inhibition of forskolinstimulated adenylate cyclase activity occurred in cell-free preparations from 1321N1 cells. The inhibitory activity of these guanine nucleotides was lost in membrane preparations from pertussis toxin-treated cells. The data suggest that adenylate cyclase is not involved in cholinergic action in 1321N1 cells and, furthermore, N. is not involved in muscarinic receptor-mediated activation of phosphodiesterase in these cells. Thus, pertussis toxin can be used to differentiate between two mechanisms of cholinergic regulation of cAMP metabolism.Activation of muscarinic cholinergic receptors results in attenuation of cAMP accumulation in intact cells and inhibition of adenylate cyclase activity in cell-free preparations (1-6). The GTP dependence of this inhibition (4, 5), the negative heterotropic effects of guanine nucleotides on agonist binding to inhibitory receptors (6-8), and knowledge of the role of the stimulatory guanine nucleotide regulatory protein (N,) in the mechanism of activation of adenylate cyclase (9) have led to the proposal that an inhibitory guanine nucleotide regulatory protein (N,) is involved in the mechanism of receptor-mediated inhibition of adenylate cyclase (10). Activation and inhibition of ade...

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“…These include opiate [ 17], muscarinic cholinergic [18], ct2-adrenergic [15] in neuroblastoma X glioma hybrids; muscarinic cholinergic in myocardium [19,20]; dopamine (via a D2 receptor) in intermediate pituitary [21 ];adenosine, PGEI and nicotinic acid in adipocytes [22][23][24]; a2-adrenergic in platelets [12,25]; opiate and adenosine in hippocampus [26]; opiates in striatum [27,28]; angiotensin and a2-adrenergic in liver [29]; and adenosine in brain cortex [30].…”

Section: Dually Regulated Adenylate Cyclase Systemsmentioning

confidence: 99%

Bimodal regulation of adenylate cyclase

Cooper

1982

FEBS Letters

161

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A physiological requirement of Na+ for the regulation of cAMP levels in intact NG108-15 cells

Cited by 32 publications

References 13 publications

Muscarinic cholinergic-receptor stimulation of specific GTP hydrolysis related to adenylate cyclase activity in canine cardiac sarcolemma.

Muscarinic cholinergic-receptor stimulation of specific GTP hydrolysis related to adenylate cyclase activity in canine cardiac sarcolemma.

Pertussis toxin differentiates between two mechanisms of attenuation of cyclic AMP accumulation by muscarinic cholinergic receptors.

Bimodal regulation of adenylate cyclase

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