Molecular Pharmacology, Vol 10, 155-161, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Guanosine Cyclic 3', 5'-Monophosphate and Guanylate Cyclase Activity in Guinea Pig Lung: Effects of Acetylcholine and Cholinesterase Inhibitors

¹ Molecular Disease Branch, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland 20014

The effects of acetylcholine, other neurotransmitters, and hormones on the guanosine cyclic 3', 5'-monophosphate and adenosine cyclic 3', 5'-monophosphate contents of guinea pig lung were investigated. When lung slices were incubated in the presence of 0.1 mM physostigmine and 1 mM theophylline (which themselves had little effect), the addition of acetylcholine produced a prompt rise in cyclic GMP concentration, which reached a maximum (about 250% of basal) in 1-3 min and began to decline by 6 min, approaching control levels in 12 min. When measured at 2 min the effect of 0.1 µM acetylcholine was negligible, and that of 1 µM was essentially maximal. Acetylcholine also increased the cyclic AMP content of lung slices 2-3-fold in 2 min. The effects on both nucleotides were prevented by 0.5 mM atropine. Prostaglandins E₁, E₂, A₂ and F₂ (2 µM), 1 µM isoproterenol, and 0.1 mM serotonin had no effect on basal cyclic GMP concentration or on the increment produced by acetylcholine. The cyclic AMP content of lung slices was markedly increased by exposure (for 2 min) to prostaglandin E₁, isoproterenol, or epinephrine. The effect of epinephrine was prevented by propranolol and unaffected by phentolamine. Neither of the adrenergic blocking agents alone or in combination with epinephrine significantly affected cyclic GMP levels. Guanylate cyclase activity assayed in whole homogenates of lung was not demonstrably affected by acetylcholine or other cholinergic agents. It was significantly increased by 1 mM physostigmine (alone or in the presence of acetylcholine) but not by other inhibitors of cholinesterase (neostigmine or edrophonium). This effect of physostigmine was not prevented by atropine.

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ACKNOWLEDGMENT J. S. was an associate in the Pharmacology Research Training Program of the National Institute of General Medical Sciences.

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