AJP - Cell Physiology, Vol 260, Issue 1 C79-C87, Copyright © 1991 by American Physiological Society

ARTICLES

Angiotensin II decreases cGMP levels in neuronal cultures from rat brain

C. Sumners and L. M. Myers
Department of Physiology, College of Medicine, University of Florida, Gainesville.

In previous studies we have determined that both cultured neuronal and astrocyte glial cells prepared from the hypothalamus and brain stem of 1-day-old rats contain specific receptors for angiotensin II (ANG II). Astrocyte glial receptors are coupled to inositol phospholipid hydrolysis, but there is little indication of the intracellular messengers or signal transduction mechanisms coupled to the neuronal ANG II receptors. In the present study, we have determined that ANG II decreases cellular guanosine 3',5'-cyclic monophosphate (cGMP) levels in neuronal but not in astrocyte glial cultures. This effect is both time and concentration dependent and is inhibited by the ANG II-receptor antagonist [Sar1,Ile8]ANG II, showing the involvement of specific ANG II receptors. ANG II has no effects on particulate or soluble guanylate cyclase activities or on efflux of cGMP from neuronal cultures. However, the effects of ANG II on cellular cGMP content are abolished by pretreatment with the calcium channel blockers cadmium and nifedipine, and by the nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. These results suggest that calcium entry and possibly activation of a phosphodiesterase enzyme are involved in this ANG II-induced effect. This represents the first demonstration of a receptor-mediated effect of ANG II on an intracellular messenger in neuronal cultures. The functional role of cGMP as an intracellular messenger coupled to ANG II receptors in cultured neurons remains to be determined.

This article has been cited by other articles:

				S. E. Abbey and L. R. Potter Vasopressin-dependent Inhibition of the C-type Natriuretic Peptide Receptor, NPR-B/GC-B, Requires Elevated Intracellular Calcium Concentrations J. Biol. Chem., November 1, 2002; 277(45): 42423 - 42430. [Abstract] [Full Text] [PDF]

				M. de Gasparo, K. J. Catt, T. Inagami, J. W. Wright, and Th. Unger International Union of Pharmacology. XXIII. The Angiotensin II Receptors Pharmacol. Rev., September 1, 2000; 52(3): 415 - 472. [Abstract] [Full Text] [PDF]

				S. Gallinat, S. Busche, M. K. Raizada, and C. Sumners The angiotensin II type 2 receptor: an enigma with multiple variations Am J Physiol Endocrinol Metab, March 1, 2000; 278(3): E357 - E374. [Abstract] [Full Text] [PDF]

				Y. Higashi, T. Oshima, S. Sasaki, Y. Nakano, M. Kambe, H. Matsuura, and G. Kajiyama Angiotensin-Converting Enzyme Inhibition, But Not Calcium Antagonism, Improves a Response of the Renal Vasculature to L-Arginine in Patients With Essential Hypertension Hypertension, July 1, 1998; 32(1): 16 - 24. [Abstract] [Full Text] [PDF]

				G. Berkenboom, D. Brekine, P. Unger, K. Grosfils, M. Staroukine, and J. Fontaine Chronic Angiotensin-Converting Enzyme Inhibition and Endothelial Function of Rat Aorta Hypertension, November 1, 1995; 26(5): 738 - 743. [Abstract] [Full Text]

				L. Caputo, J. Benessiano, C. M. Boulanger, and B. I. Levy Angiotensin II Increases cGMP Content Via Endothelial Angiotensin II AT1 Subtype Receptors in the Rat Carotid Artery Arterioscler. Thromb. Vasc. Biol., October 1, 1995; 15(10): 1646 - 1651. [Abstract] [Full Text]