Molecular Pharmacology, Vol 13, 330-341, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Regulation of Adenosine Cyclic 3',5'-Monophosphate and Guanosine Cyclic 3',5'-Monophosphate Levels and Contractility in Bovine Tracheal Smooth Muscle

¹ Division of Clinical Pharmacology, Departments of Internal Medicine and Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22903

The effects of various agents on cyclic 3',5'-AMP and cyclic 3',5'-GMP levels and mechanical activity of bovine tracheal smooth muscle were examined. Carbachol, acetylcholine, and histamine caused muscle contraction and increased cyclic GMP levels several fold in a dose-dependent manner; contraction preceded the increase in cyclic GMP. Serotonin and high K⁺ concentrations contracted muscle to the same degree as carbachol, while cyclic GMP increases were smaller than that due to carbachol. The effects of carbachol and histamine were blocked by atropine and diphenhydramine, respectively. The calcium ionophore A-23187 also increased cyclic GMP levels and caused contraction. Guanylate cyclase activators-sodium azide, hydroxylamine, sodium nitrite, nitroglycerin, and sodium nitroprusside-increased cyclic GMP levels and relaxed tracheal smooth muscle. None of these agents had any effect on cyclic AMP levels. The presence of Ca²⁺ in the incubation medium was not required for cyclic GMP increases with these latter agents. However, it was required in order to see increases in cyclic GMP with carbachol, histamine, and A-23187. Adremergic agonists relaxed muscle preparations and increased cyclic AMP levels 2-3-fold. Both these effects were blocked by propranolol. Inhibitors of cyclic nucleotide phosphodiesterases relaxed muscle preparations and were associated with increases in both cyclic AMP and cyclic GMP. Prostaglandins E₁ and F₂ had little or no effect on mechanical activity or cyclic nucleotide levels. The addition of 1 mM 8-bromo-cyclic GMP or 8-bromo-AMP relaxed muscle preparations. A variety of other nucleotides had no effect. These results support the hypothesis that cyclic AMP plays a role in relaxation of tracheal muscle induced by adrenergic agents. However, with a variety of other agents, we found that contraction or relaxation occurred with increases either in cyclic GMP alone or in both cyclic AMP and cyclic GMP. Thus the roles of cyclic AMP and cyclic GMP in smooth muscle mechanical activity remain obscure.

Note:
ACKNOWLEDGMENTS We thank Daniel Macklin and Joanne Holmes for their technical assistance, and Cathy Bostron for typing this manuscript.

This article has been cited by other articles:

				L. P. Coelho, M. F. Serra, A. L. de Aguiar Pires, R. S. B. Cordeiro, P. M. R. e Silva, M. H. dos Santos, and M. A. Martins 7-Epiclusianone, a Tetraprenylated Benzophenone, Relaxes Airway Smooth Muscle through Activation of the Nitric Oxide-cGMP Pathway J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 206 - 214. [Abstract] [Full Text] [PDF]

				J. George, I. Kitzis, D. Zandorf, M. Golovner, I. Shapira, S. Laniado, and A. Roth Safety of Nitrate Withdrawal in Angina-Free and Hemodynamically Stable Patients With Coronary Artery Disease Chest, November 1, 2003; 124(5): 1652 - 1657. [Abstract] [Full Text] [PDF]

				A. Borges, S. Sanchez de Villarroel, N. J. Winand, I. Lippo de Becemberg, M. J. Alfonzo, and R. Gonzalez de Alfonzo Molecular and Biochemical Characterization of a CNP-Sensitive Guanylyl Cyclase in Bovine Tracheal Smooth Muscle Am. J. Respir. Cell Mol. Biol., July 1, 2001; 25(1): 98 - 103. [Abstract] [Full Text] [PDF]

				F. Petak, J. L. Wale, and P. D. Sly Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats J Appl Physiol, October 1, 1999; 87(4): 1373 - 1380. [Abstract] [Full Text] [PDF]

				H. Y. Qiu, D. Henrion, J. Benessiano, C. Heymes, B. Tournier, and B. I. Levy Decreased Flow-Induced Dilation and Increased Production of cGMP in Spontaneously Hypertensive Rats Hypertension, December 1, 1998; 32(6): 1098 - 1103. [Abstract] [Full Text] [PDF]

				J. D. Parker and J. O. Parker Nitrate Therapy for Stable Angina Pectoris N. Engl. J. Med., February 19, 1998; 338(8): 520 - 531. [Full Text] [PDF]

				A. M. Hamad, S. Range, E. Holland, and A. J. Knox Regulation of cGMP by soluble and particulate guanylyl cyclases in cultured human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, October 1, 1997; 273(4): L807 - L813. [Abstract] [Full Text] [PDF]

				P. F. Pratt, M. Rosolowsky, and W. B. Campbell Mediators of Arachidonic Acid–Induced Relaxation of Bovine Coronary Artery Hypertension, July 1, 1996; 28(1): 76 - 82. [Abstract] [Full Text]

				F. Murad, D. Leitman, S. Waldman, C.-H. Chang, M. Hirata, and K. Kohse Effects of Nitrovasodilators, Endothelium-dependent Vasodilators, and Atrial Peptides on cGMP Cold Spring Harb Symp Quant Biol, January 1, 1988; 53(0): 1005 - 1009. [Abstract] [PDF]

				P de Lanerolle, M Nishikawa, D. Yost, and R. Adelstein Increased phosphorylation of myosin light chain kinase after an increase in cyclic AMP in intact smooth muscle Science, March 30, 1984; 223(4643): 1415 - 1417. [Abstract] [PDF]

				W. Arnold, R Aldred, and F Murad Cigarette smoke activates guanylate cyclase and increases guanosine 3',5'-monophosphate in tissues Science, December 2, 1977; 198(4320): 934 - 936. [Abstract] [PDF]