The effect of oxotremorine and atropine on cGMP and cAMP levels in mouse cerebral cortex and cerebellum

Ferrendelli, James A.; Steiner, Alton L.; McDougal, David B.; Kipnis, David

doi:10.1016/0006-291x(70)90193-2

Cited by 220 publications

(49 citation statements)

References 3 publications

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“…Such action of prostaglandin El is also obviated by noradrenaline [5] and morphine [8,19], 2 agents known to increase the intraceUular levels of cyclic GMP [11,20] in the hybrids. Cholinergic agonists increase the level of cyclic GMP in heart [22,23], brain [23][24][25], liver and thyroid [26], ileum [25], vas deferens [27], fat cells [28] and lung [29] and partially prevent the increase of the concentration of cyclic AMP by isoproterenol or glucagon in heart [30] or by adrenaline in uterus [31].…”

Section: Discussionmentioning

confidence: 99%

Effects of cholinergic agents and sodium ions on the levels of guanosine and adenosine 3′:5′‐cyclic monophosphates in neuroblastoma and neuroblastoma x glioma hybrid cells

et al. 1975

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Section: Discussionmentioning

confidence: 99%

Effects of cholinergic agents and sodium ions on the levels of guanosine and adenosine 3′:5′‐cyclic monophosphates in neuroblastoma and neuroblastoma x glioma hybrid cells

et al. 1975

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“…Kaliner et al (4) have recently shown that human lung tissue involved in release of immediate hypersensitivity mediators have cAMP-independent cholinergic receptors; cholinergic agonists, when given in optimal dosages remarkably similar to those used in the present study, caused increased secretion of histamine and Slow Reacting Substance of Anaphylaxis-A; treatment of lung tissue with 8-bromocyclic GMP resulted in increased mediator release. Furthermore, cholinergic stimulation of heart and brain elevates intracellular cGMP (5,14,15). Franks and McManus (16) have reported that hydrolysis of cAMP by phosphodiesterase is enhanced by a narrow concentration of cGMP in an in vitro system.…”

Section: Methodsmentioning

confidence: 99%

Alteration of the Cytotoxic Action of Sensitized Lymphocytes by Cholinergic Agents and Activators of Adenylate Cyclase

Strom

Deisseroth²,

Morganroth³

et al. 1972

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

128

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The cytotoxic action of lymphocytes upon cells bearing alloantigens to which they are sensitized is inhibited by agents that elevate intracellular amounts of 3': 5'-cyclic AMP: prostaglandin El, cholera toxin, and theophylline. Cholinergic agents, added in the range of 1 to 100 pM, enhance cytotoxicity, an effect that is blocked by atropine. Because 2995After exsanguination of rats by aortic puncture, sensitized recipient spleen tissue and normal thymus tissue from the donor strain were excised and placed in RPMI-1640 medium containing 0.5 volume percent of 1 M HEPES buffer (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, pH 7.55) and 4% (v/v) of heat-inactivated fetal-calf serum. The organs were gently expressed through a fine steel mesh, and the cell suspensions were passed through a tube containing cotton; medium was added liberally. Subsequently, the cell suspensions were purified by Ficoll-Hypaque gradient separation (7), resulting in suspensions consisting almost exclusively of viable lymphocytes. After it was washed, 1.5 ml of the thymic cell suspension containing 1-3 X 107 cells was incubated with 300 ,uCi 5"Cr for 1 hr before it was washed twice with medium and centrifuged at 200 X g to remove free "Cr. Before the spleen and thymus cells were counted in a Coulter counter, they were suspended in RPMI-1640 medium to which 10% (v/v) heat-inactivated fetal-calf serum and 0.5 volume of 1 li HEPES buffer were added. The concentration of the suspension of spleen cells was adjusted to 5 X 10' cells per ml.Lymphocyte-mediated cytotoxicity was quantitated by a modification of Brunner's method (1). Attacking cell populations consisted of sensitized (by LBN skin grafting) or unsensitized Lewis spleen cells, and target cells were "Cr-labeled thymocytes. All media and cell mixtures were suspended in disposable 10 X 75-mm glass test tubes in triplicate. Incubations containing 5 X 104 target cells suspended in 2 ml of RPMII-1640 media with 10% (v/v) heat-inactivated fetalcalf serum and 0.5 volume percent 1 M HEPES buffer were used as controls to determine spontaneous "Cr release. 5 X 106 sensitized or unsensitized Lewis cells were added to 5 X 104 target cells in a final medium volume of 2 ml. After incubation at 370 for 30 min, all mixtures were centrifuged at 50 X g for 10 min in order to promote close cell contact. The mixtures were further incubated for 3.5 hr at 370, then centrifuged at 400 X g for 10 min. The supernatants were promptly decanted into disposable 13 X 100-mm glass test tubes and counted for "Cr release. In studies with pharmacological agents, 0.1 ml of the agent was added to triplicate control samples containing target cells alone and to triplicate samples of mixtures of attacking and target cells. 2-ml Suspensions of 5 X 104 target cells were frozen and thawed in a dry ice-ethanol bath three times to determine maximum releasable cell-bound chromium. None of the pharmacological

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“…Recent studies indicate that acetylcholine can cause the accumulation of cyclic GMP in heart (10, 11), brain (11,12), and ductus deferens (13). Perfusion of isolated rat heart with acetylcholine caused an increase of up to 140% in cyclic GMP content (10).…”

mentioning

confidence: 99%

Role of Muscarinic Cholinergic Receptors in Regulation of Guanosine 3′:5′-Cyclic Monophosphate Content in Mammalian Brain, Heart Muscle, and Intestinal Smooth Muscle

Lee

Kuo

Greengard

1972

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

287

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Effects of acetylcholine and of agents that mimic or block its physiological actions have been studied upon concentrations of guanosine 3':5'-cyclic monophosphate (cyclic GMP) and adenosine 3':5'-cyclic monophosphate (cyclic AMP) in slices of mammalian cerebral cortex, heart ventricle, and ileum. Acetylcholine, and cholinomimetic agents with a predominantly muscarinic action, such as methacholine, bethanechol, and pilocarpine, induced an increase in the concentration of cyclic GMP, accompanied by no change or a slight decrease in the concentration of cyclic AMP, in all three tissues studied. Tetramethylammonium, a cholinomimetic agent with a predominantly nicotinic action, on the other hand, did not significantly alter concentrations of either cyclic GMP or cyclic AMP. The increase in the tissue content of cyclic GMP induced by acetylcholine and its muscarinic analogs was antagonized by atropine, a muscarinic blocking agent, but not by hexamethonium, a nicotinic blocking agent.These and other results suggest the generalization that the interaction of acetylcholine with muscarinic receptors, but not with nicotinic receptors, causes an increase in the concentration of cyclic GMP. The data are compatible with the hypothesis that cyclic GMP may mediate the muscarinic actions of acetyicholine.The antagonistic actions of cholinergic and adrenergic agents on the physiology of contraction of intestinal smooth muscle and of cardiac muscle are reflected in, and may result from, antagonistic actions of these compounds on the levels of both cyclic GMP and cyclic AMP in these tissues.A substantial amount of evidence now exists indicating that several hormones and neurotransmitter agents may exert their biological actions by altering the amount of adenosine 3':5'-monophosphate (cyclic AMP) in target cells. In recent years, the possibility has been raised that guanosine 3':5'-cyclic monophosphate (cyclic GMP) may also play a significant role in the regulation of metabolism and function in animal tissues. Cyclic GMP has been found in tissues and fluids of several species (e.g., 1-4), and enzymes have been found that catalyze the synthesis (4, 5) and breakdown (6) of cyclic GMP. In addition, a family of protein kinases has been found that is specifically activated by cyclic GMP (7-9), rather than by cyclic AMP, and it has been proposed (7) that the biological effects of cyclic GMP are mediated through this family of protein kinases (7-9). Nevertheless, little is known about the factors that regulate the concentration of cyclic GMP in tissues or about the nature of the biological effects that may be regulated by cyclic GMP.Recent studies indicate that acetylcholine can cause the accumulation of cyclic GMP in heart (10, 11), brain (11, 12), and ductus deferens (13). Perfusion of isolated rat heart with acetylcholine caused an increase of up to 140% in cyclic GMP content (10). Moreover, application of low concentrations of acetylcholine to slices of rat heart caused increases of up to 10-fold in the concentration of cyclic ...

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The effect of oxotremorine and atropine on cGMP and cAMP levels in mouse cerebral cortex and cerebellum

Cited by 220 publications

References 3 publications

Effects of cholinergic agents and sodium ions on the levels of guanosine and adenosine 3′:5′‐cyclic monophosphates in neuroblastoma and neuroblastoma x glioma hybrid cells

Effects of cholinergic agents and sodium ions on the levels of guanosine and adenosine 3′:5′‐cyclic monophosphates in neuroblastoma and neuroblastoma x glioma hybrid cells

Alteration of the Cytotoxic Action of Sensitized Lymphocytes by Cholinergic Agents and Activators of Adenylate Cyclase

Role of Muscarinic Cholinergic Receptors in Regulation of Guanosine 3′:5′-Cyclic Monophosphate Content in Mammalian Brain, Heart Muscle, and Intestinal Smooth Muscle

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