Effects Of Dibutyryl Cyclic GMP Research Articles

Stimulatory effect of dibutyryl cyclic GMP on acid secretion in mouse isolated stomach and on histamine release in gastric mucosal cells

We previously reported that endogenous nitric oxide (NO) is involved in the peripheral control of gastric acid secretion induced by some secretagogues, and that endogenous NO is involved in the acid secretion process via histamine release from histamine-containing cells. However, the stimulus-secretion coupling in the cells remains to be clarified. In the present study, we investigated the effect of dibutyryl cyclic GMP on gastric acid secretion in mouse isolated stomach and on histamine release in gastric mucosal cells, in comparison with those of dibutyryl cyclic AMP. Dibutyryl cyclic GMP (300 μM) produced a slight but significant increase of gastric acid secretion, which was completely inhibited by the histamine-H2 receptor antagonist famotidine. In contrast, dibutyryl cyclic GMP (1 mM) markedly inhibited histamine-induced acid secretion. Dibutyryl cyclic AMP (100 μM) produced a sustained increase of gastric acid secretion. The pretreatment with famotidine partially inhibited dibutyryl cyclic AMP-induced gastric acid secretion. Dibutyryl cyclic GMP and dibutyryl cyclic AMP significantly increased the histamine release from gastric mucosal cells. These results suggest that both intracellular cyclic GMP and cyclic AMP act as second messengers for histamine release in the histamine-containing cells, probably ECL cells. On the other hand, in gastric parietal cells, cyclic AMP has a stimulatory effect on gastric acid secretion, whereas cyclic GMP has an inhibitory effect.

Cyclic GMP inhibition of stimulated phosphoinositide hydrolysis in neuronal cultures.

We used a radioreceptor binding assay to analyse the effect of dibutyryl cyclic GMP (dbcGMP) and the nitric oxide (NO) donor sodium nitroprusside (SNP) on inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) mass accumulation in response to the muscarinic receptor agonist carbachol and K(+)-induced depolarization in neuronal primary cultures. In forebrain neurones carbachol induced a transient rise in Ins(1,4,5)P3 with a maximal increase of about 2.5-fold at 5 s. At this time 30 mM K+ induced a somewhat lower stimulation. Both carbachol and high K+ stimulations were significantly inhibited by dbcGMP and by SNP. The effect of SNP was blocked by haemoglobin. dbcGMP inhibition of the carbachol effect was also observed in cerebellar granule cell cultures. These results show for the first time that the NO/cGMP generating system can modulate phosphoinositide turnover in CNS neurones in a manner similar to that previously reported to occur in peripheral neurones and non-neuronal tissues.

Peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway

We have previously described the analgesic effect of dibutyryl cyclic GMP or acetylcholine (ACh) injected into rat paws. Since ACh induces nitric oxide (NO) release from endothelial cells, we investigated the possible involvement of the NO-cyclic GMP pathway in ACh-induced analgesia, using a modification of the Randall-Selitto rat paw test. We found that sodium nitroprusside, which releases NO non-enzymatically, caused antinociception in the rat paw made hyperalgesic with prostaglandin E 2. The analgesic effect of sodium nitroprusside and ACh was enhanced by intraplantar injection of an inhibitor of cyclic GMP phosphodiesterase (MY 5445) and was blocked by a guanylate cyclase inhibitor, methylene blue (MB). The analgesia induced by ACh, but not by sodium nitroprusside, was blocked by N G-monomethyl-L-arginine (L-NMMA), an inhibitor of the formation of NO from L-arginine. L-arginine itself had little or no effect upon prostaglandin-induced hyperalgesia but caused significant analgesia in paws inflamed with carrageenin. This analgesia was blocked by MB, as well as by L-NMMA, and was potentiated by MY 5445. These results suggest that ACh-induced analgesia was mediated via the release of NO. The results also indicate that the guanylate cyclase system is stimulated in the inflammatory reaction. The analgesia resulting from activation of this system is possibly overshadowed by substances that concomitantly stimulate nociceptor hyperalgesic mechanisms.

Antagonistic effect of dibutyryl cyclic GMP on caerulein induced insulin secretion in isolated perifused rat islets.

The effects of caerulein and dibutyryl cyclic GMP on isolated rat islets were studied using the perifusion system. One, 20, 50 and 100 nM caerulein stimulated insulin secretion in the perifused rat islets, in a dose dependent manner. Insulin secretion reached a maximal level in the presence of 50 nM caerulein. Caerulein-induced insulin secretion showed a predominant first and minimal second phase. After cessation of stimulation with 50 nM caerulein, the insulin secretion level did not return to the basal value, but enhanced hormone secretion was sustained to a significant extent (p less than 0.01). The simultaneous administration of 10(-3) M dibutyryl cyclic GMP, a specific membrane antagonist against cholecystokinin (CCK), inhibited the first and second phases of caerulein-induced insulin secretion. Moreover, with this nucleotide, "persistent" insulin secretion induced by 50 nM caerulein was inhibited. These data indicate that caerulein directly stimulates pancreatic B cells and that this peptide causes "persistent" insulin secretion. Dibutyryl cyclic GMP counteracts the effects of caerulein. Thus, both pancreatic B cells and pancreatic acinar cells possibly possess a CCK receptor.

Antagonistic effect of dibutyryl cyclic GMP on caerulein induced insulin secretion in isolated perifused rat islets

Antagonistic effect of dibutyryl cyclic GMP on caerulein induced insulin secretion in isolated perifused rat islets

Differences between muscular receptors and neurnal receptors for cholecystokinin-octapeptide in the guinea-pig gallbladder

To investigate the differences between muscular and neural receptors for cholecystokinin-octapeptide (CCK-OP) in the guinea-pig gallbladder, we studied the effects of dibutyryl cyclic GMP (dbc GMP) on CCK-OP-evoked contraction and [ 3H]acetylcholine (ACh) release. 10 −3 M dbc GMP significantly reduced CCK-OP (10 −8 M)-evoked contractions without affecting the peptide-induced [ 3H]ACh release. It is suggested that there are two types of CCK-OP receptors in the guinea-pig gallbladder (dbc GMP-sensitive muscular receptors and dbc GMP-insensitive neural receptors).

Hemodynamic effects of dibutyryl cyclic GMP in anesthetized dogs.

Dibutyryl cyclic GMP was given intravenously to anesthetized dogs with doses of 0.0625, 0.125, 0.25, 0.5 and 1.0 mg/kg, respectively. It induced decreases in blood pressure, heart rate, max LV dp/dt and total peripheral resistance with increase of stroke volume in a dose-dependent manner. Although these effects began to appear 30 sec after the administration in each dose, the duration of the effect was observed 50 sec after the administration. Effects of 1 mg/kg dibutyryl cyclic GMP on mean blood pressure and max LV dp/dt were almost equal to those of 3 micrograms/kg acetylcholine, but dibutyryl cyclic GMP was revealed to have a slower onset and longer acting effects than acetylcholine. The administration of atropine did not block the effect of dibutyryl cyclic GMP but blocked those of acetylcholine. These results indicate that dibutyryl cyclic GMP does not exert these effects through muscarinic receptors in spite of its acetylcholine-like effects.

Effects of dibutyryl cyclic GMP (DBcGMP) on canine cardiovascular system : K.Imura, K.Ogawa, T.Satake. The 2nd Department of Internal Medicine Nagoya University School of Medicine, Nagoya Japan

Effects of dibutyryl cyclic GMP (DBcGMP) on canine cardiovascular system : K.Imura, K.Ogawa, T.Satake. The 2nd Department of Internal Medicine Nagoya University School of Medicine, Nagoya Japan

Regulation of the macromolecular transport in the brain microvessels: The role of cyclic GMP

The possible effects of dibutyryl cyclic GMP (db-cGMP), the lipid-soluble derivative of cyclic GMP, on brain microvessels were studied by light microscopic detection of albumin and quantitative electron microscopy. Different concentrations (25, 50, 100 and 200 micrograms) of db-cGMP were given to adult rats by intracarotid infusion, while in the controls, the animals were infused either with Krebs-Ringer solution or with the same solution containing butyrate or cyclic GMP. In contrast to the controls, db-cGMP was found to be able to increase the permeability of brain microvessels to albumin in a dose-dependent manner. At the same time, the number of transport vesicles being indicative of the pinocytotic activity of the endothelial cells was also increased. These results indicate that, similarly to the cyclic AMP whose effects have been revealed earlier, the cyclic GMP-system may also be involved in the regulation of opening mechanisms of the blood-brain barrier.

Potassium stimulated 45Ca uptake by cortical slices of rat brain: effects of cyclic nucleotide derivatives

The effects of dibutyryl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by cortical slices of rat brain were investigated. db-cAMP specifically inhibited the initial rate of potassium-stimulated 45Ca uptake in a dose-dependent manner. Our findings supported the suggestion that cyclic GMP may play a regulatory role in depolarization-elicited Ca 2+ influx in nerve endings in situ.

Opposite effects of dibutyryl cyclic GMP and bibutyryl cyclic AMP on glucose 1,6-diphosphate levels and the activities of glucose 1,6-diphosphate phosphatase and phosphofructokinase in diaphragm muscle

FEBS LettersVolume 115, Issue 2 p. 197-200 Full-length articleFree Access Opposite effects of dibutyryl cyclic GMP and bibutyryl cyclic AMP on glucose 1,6-diphosphate levels and the activities of glucose 1,6-diphosphate phosphatase and phosphofructokinase in diaphragm muscle Rivka Beitner, Rivka Beitner Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this authorTamar J. Cohen, Tamar J. Cohen Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this author Rivka Beitner, Rivka Beitner Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this authorTamar J. Cohen, Tamar J. Cohen Department of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelSearch for more papers by this author First published: June 30, 1980 https://doi.org/10.1016/0014-5793(80)81167-7Citations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 L.F. Leloir, R.E. Trucco, C.E. Cardini, A.C. Paladini, R. Caputto, Arch. Biochem., 19, (1948), 339– 340. 2 R. Caputto, L.F. Leloir, R.E. Trucco, C.E. Cardini, A.C. Paladini, Arch. Biochem., 18, (1948), 201– 203. 3 C.E. Cardini, A.C. Paladini, R. Caputto, L.F. Leloir, R.E. Trucco, Arch. Biochem., 22, (1949), 87– 99. 4 R. Beitner, Trends Biochem. Sci., 4, (1979), 228– 230. 5 H.W. Hofer, D. Pette, Hoppe-Seyler's Z. Physiol. Chem., 349, (1968), 1378– 1392. 6 J. Krzanowski, F.M. Matschinsky, Biochem. Biophys. Res. Commun., 34, (1969), 816– 823. 7 R. Beitner, S. Haberman, T. Cycowitz, Biochim. Biophys. Acta, 482, (1977), 330– 340. 8 R. Beitner, S. Haberman, J. Nordenberg, Mol. Cell. Endocrinol., 10, (1978), 135– 147. 9 R. Beitner, T.J. Cohen, IRCS Med. Sci., 7, (1979), 24– 10 R. Beitner, J. Nordenberg, IRCS Med. Sci., 7, (1979), 136– 11 R. Beitner, J. Nordenberg, T.J. Cohen, FEBS Lett., 104, (1979), 244– 248. 12 N.D. Goldberg, M.K. Haddox, S.E. Nicol, D.B. Glass, C.H. Sanford, F.A. Kuehl Jr., R. Estensen, G.I. Drummond Advances in Cyclic Nucleotide Research 5, (1975), Raven, New York 307– 330. 13 R. Beitner, N. Kalant, J. Biol. Chem., 246, (1971), 500– 503. 14 J.V. Passonneau, O.H. Lowry, D.W. Schulz, J.G. Brown, J. Biol. Chem., 244, (1969), 902– 909. 15 R. Beitner, T.J. Cohen, J. Nordenberg, S. Haberman, Biochim. Biophys. Acta, 586, (1979), 266– 277. 16 O.H. Lowry, N.J. Rosebrough, A.L. Farr, R.J. Randall, J. Biol. Chem., 193, (1951), 265– 275. 17 R. Beitner, S. Haberman, J. Nordenberg, T.J. Cohen, Biochim. Biophys. Acta, 542, (1978), 537– 541. 18 R. Beitner, J. Nordenberg, FEBS Lett., 98, (1979), 199– 202. Citing Literature Volume115, Issue2June 30, 1980Pages 197-200 ReferencesRelatedInformation

Inhibitory effect of dibutyryl cyclic GMP on potassium-stimulated 45Ca uptake by synaptosomes from rat brain

The effects of dibutyryl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by the P 2 fraction of Gray and Whittaker were investigated with the following results. (1) db-cGMP inhibited the initial rate of potassium-stimulated 45Ca-uptake in a dose-dependent manner in 0.1 mM Ca 0 medium, but had no effect on the uptake in low K + medium. In 0.1 mM Ca 0 medium, the concentration of db-cGMP causing 50% inhibition was about 3 mM. db-cAMP (5 mM) had no effect on the uptake. (2) db-cGMP inhibited potassium-stimulated 45Ca uptake in 1 mM Ca 0 medium, though less than in 0.1 mM Ca 0 medium. (3) db-cGMP inhibited potassium-stimulated 45Ca uptake by synaptosomes (pinched-off nerve terminals) more than the uptakes by other subfractions of P 2 fraction. It is suggested from the results that cGMP inhibits the Ca influx resulting from depolarization of the nerve endings in situ.

Guanosine 3′,5′-Monophosphate: A Central Nervous System Regulator of Analgesia

The dibutyryl derivative of guanosine 3',5'-monophosphate (cyclic GMP), administered centrally, totally abolishes response to noxious stimuli without depressing the central nervous system. Analgesic properties of the nucleotide are not reversed by naloxone. Microinjected intracerebrally into different sites, dibutyryl cyclic GMP does not mimic the action of morphine. Pharmacological effects of dibutyryl cyclic GMP suggest that endogenous cyclic GMP modulates an inhibitory pain pathway distinct from that on which morphine acts.

Direct postsynaptic membrane effect of dibutyryl cyclic GMP on mammalian sympathetic neurons

Acetylcholine and dibutyryl-guanosine 3′:5′-cyclic monophosphate (DbcGMP) were applied iontophoretically from double barreled micropipettes to the isolated rabbit superior cervical ganglion cells and the responses were recorded by intracellular microelectrode techniques. DbcGMP consistently evoked a membrane depolarization of low amplitude and long duration; in many cells, a long after-hyperpolarization was observed following the membrane depolarization. The DbcGMP-induced membrane potential change was not appreciably affected by superfusing the ganglion with d-tubocurarine and/or atropine, or by a low Ca 2+/high Mg solution. The present study demonstrates that the membrane effect of DbcGMP is exerted on postganglionic neurons.