Possible Role Of Cyclic GMP Research Articles

A Possible Role of Cyclic GMP in Membrane Fusion of Chick Embryonic Myoblasts in Culture

A Possible Role of Cyclic GMP in Membrane Fusion of Chick Embryonic Myoblasts in Culture

Use of the cell-attached patch clamp technique to examine regulation of single cardiac K channels by cyclic GMP

Cyclic nucleotides play a central role in the modulation of ion channels in a variety of tissues, including the heart. In order to determine the possible role of cyclic GMP (cGMP) in the regulation of the background K channel activity of cardiac cells, the effect of 8-Br-cGMP on the inwardly-rectifying K channels of cultured ventricular myocytes from embryonic chick hearts was examined. 8-Br-cGMP (10(-4) to 10(-3) M) inhibited these single channel currents within 3 to 10 min. Spontaneous recovery of the currents occurred with prolonged (greater than or equal to 15 min) exposure to 8-Br-cGMP, but this recovery was accompanied by altered channel behavior. Thus, a new long-lasting open state of the channel appeared, in addition to the open state observed prior to 8-Br-cGMP addition. Superfusion of the cells with the muscarinic agonist carbamylcholine (10(-5) M) also resulted in inhibition of the currents, which suggests that the cGMP-mediated inhibition of these channels may occur under physiological conditions. Thus, it appears that cGMP may be an important modulator of the background K conductance (and excitability) of cardiac cells.

Stimulatory effects of muramyl dipeptide and its butyl ester derivative on the proliferation and activation of macrophages in vitro

Muramyl dipeptide (MDP) and the butyl ester derivative, N- acetylmuramyl- l-alanyl- d-glutamine-alpha -n- butyl ester (MDP[Gln]OnBu), were shown to induce the in vitro proliferation of oil-induced guinea pig peritoneal exudate cells (PEC). Both agents induced 10–20 fold increases in tritiated thymidine incorporation in PEC cultures. The maximal effects occurred in 72 h cultures stimulated with either 0.1 μg MDP or 10 μg MDP[Gln]OnBu. The mitogenic effects of MDP appeared to be mediated by a macrophage product detected in the supernatants of MDP-stimulated cultures. Supernatants of MDP- or MDP[Gln]OnBu-stimulated PEC cultures were also inhibitory to normal fibroblast growth and cytotoxic to L929 tumor cells. These results indicated that these agents may stimulate macrophages by modulating secretory functions. In addition, either peptidoglycan was capable of activating bactericidal activity in in vitro macrophage cultures. Initial studies of possible mechanisms of action revealed an early increase in the level of cyclic GMP. The possible role of cyclic GMP in mediating the stimulation of macrophage secretory processes is discussed.

A comparison of the effects of sodium nitroprusside and insulin on the control of metabolism in rat isolated adipocytes

Sodium nitroprusside, a known activator of guanylate cyclase within cells, was used as a probe to investigate the possible role of cyclic GMP in the control of metabolism within rat isolated white adipocytes. Over the concentration range 0–0.1 mM, it increased intracellular cyclic GMP concentrations up to 6-fold within 2 min. Over the same concentration range, it increased the incorporation of 14C from d-[U- 14C]glucose into triacylglycerol and of l-[ 14C]leucine into protein. It also inhibited adrenalin-stimulated lipolysis in the cells, but had no effect on the transport of glucose into the cells. The effects of sodium nitroprusside were compared with those elicited by insulin under identical conditions, as this hormone was shown to cause a similar, but transient, rise in intracellular cyclic GMP concentrations within these cells. Nor insulin, neither sodium nitroprusside were able to increase cyclic AMP levels in adipocytes, whereas adrenalin (0.3 μM) stimulated this production. It is suggested that cyclic GMP may have a role in the control of some part of metabolism ‘glucose or amino acids’ in adipocytes, and that sodium nitroprusside is a useful probe to investigate this. The limitation of its use are discussed.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

Cyclic guanosine 3′,5′-monophosphate and phosphodiesterase activity in mitogen-stimulated human lymphocytes

The cyclic adenosine 3′,5′-monophosphate (cyclic AMP) phosphodiesterase from human leukemic lymphocytes differes from the normal cell enzyme in having a much higher activity and a loss of inhibition by cyclic guanosine 3′,5′-monophosphate (cyclic GMP). In an effort to determine the mechanism of these alterations, we have studied this enzyme in a model system, lectin-stimulated normal human lymphocytes. Following stimulation of cells with concanavalin A (con A) the enzyme activity gradually becomes altered, until it fully resembles the phosphodiesterase found in leukemic lymphocytes. The changes in the enzyme parallel cell proliferation as measured by increases in thymidine incorporation into DNA. The addition of a guanylate cyclase inhibitor preparation from the bitter melon prevents both the changes in the phosphodiesterase and the thymidine incorporation into DNA. This blockage can be partially reversed by addition of 8-bromo cyclic guanosine 3′,5′-monophosphate (8-bromo cyclic GMP) to the con A-stimulated normal lymphocytes. These results indicate a possible role of cyclic GMP in a growth related alteration of cyclic AMP phosphodiesterase.

Inhibition of toad urinary bladder sodium transport by carbamylcholine: possible role of cyclic GMP

Page F586: M. K. Sahib, J. H. Schwartz, and J. S. Handler. “Inhibition of toad urinary bladder sodium transport by carbamylcholine: possible role of cyclic GMP.” In Table 3 (page F589) the values 11.9 ± 0.6 for cAMP and 0.28 ± 0.02 for cGMP should be opposite 10 mU/ml AVP plus 100 μM carbamylcholine. Braces have been added to the table to define the paired experiments. The corrected table follows. (See PDF)

Rapid rise in cyclic GMP accompanies catecholamine secretion in suspensions of isolated adrenal chromaffin cells

Acetylcholine stimulates a five-fold increase in cyclic GMP within seconds of addition to suspensions of isolated adrenal chromaffin cells. The rapid kinetics and dose-response curve for cyclic GMP accumulation are compared with corresponding results for catecholamine secretion and a possible role of cyclic GMP in stimulus-secretion coupling is considered.

Distribution of Cyclic Nucleotides in the Organ of Corti

Recent developments in radioimmunoassay technology have made possible measurements of cyclic nucleotides in individual specimens of the organ of Corti and its subdivisions. Steep longitudinal and transverse gradients of glycogen are known to exist in the organ of Corti of the guinea pig, with preferential accumulation in the outer hair cells of the apical turns. However, no significant longitudinal gradient of cyclic AMP was detectable in the organ of Corti, and the concentration of the compound was found to be nearly equal in the inner and outer hair cell layers. This is indirect evidence against the concept that cyclic AMP plays a role as "second messenger" in the control of glycogen metabolism of the organ of Corti. By contrast, the concentration of cyclic GMP was found to be consistently higher in the inner layer than in the outer layer of the organ of Corti, and to increase significantly in basal direction. This trend is remarkably similar to the distribution patterns of acetylcholinesterase, which may be considered as indirect evidence in favor of a possible role of cyclic GMP in the mediation of cholinergic effects.

Inhibition of toad urinary bladder sodium transport by carbamylcholine: possible role of cyclic GMP.

ARTICLESInhibition of toad urinary bladder sodium transport by carbamylcholine: possible role of cyclic GMPM. K. Sahib, J. H. Schwartz, and J. S. HandlerM. K. Sahib, J. H. Schwartz, and J. S. HandlerPublished Online:01 Dec 1978https://doi.org/10.1152/ajprenal.1978.235.6.F586MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByCholinergic inhibition of electrogenic sodium absorption in the guinea pig distal colonHisayoshi Hayashi, Tomoko Suzuki, Takeshi Yamamoto, and Yuichi Suzuki1 April 2003 | American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 284, No. 4 More from this issue > Volume 235Issue 6December 1978Pages F586-F591 Copyright & PermissionsCopyright © 1978 the American Physiological Societyhttps://doi.org/10.1152/ajprenal.1978.235.6.F586PubMed83797History Published online 1 December 1978 Published in print 1 December 1978 Metrics

The influence of histamine on epithelial cell proliferation in the jejunum of the rat.

1. The influence of histamine and histamine receptor blockade on the mitotic rate in epithelial cell proliferation in epithelial cells lining the crypts of Lieberkühn in rat jejunum was studied. 2. Histamine injection resulted in an increase in the mitotic rate. This increase in mitotic rate was blocked by metiamide but not by mepyramine. 3. Prevention of histamine synthesis by alpha-methylhistidine administration did not alter the mitotic rate. 4. The mechanism by which histamine may influence crypt cell proliferation and possible role of cyclic GMP in this mediation are discussed.¿

Guanylate cyclase and cyclic-GMP phosphodiesterase activities in mammary glands of mice during pregnancy and lactation.

Guanylate cyclase and cyclic-GMP phosphodiesterase activities were measured in homogenates of mammary glands from virgin, pregnant, and lactating mice. Guanylate cyclase activities increased 35% in mammary tissues during pregnancy, and a further 40% increase was observed during lactation. Cyclic-GMP phosphodiesterase activity also increased during pregnancy but activities were not different in glands from lactating mice vs glands from pregnant mice. These results are discussed with regard to a possible role of cyclic-GMP in regulating lactational processes.