Absence of effects of dibutyryl cyclic guanosine 3′,5′-monophosphate on release of α-amylase,45Ca efflux,and protein synthesis in rat pancreas in vitro

Summary Dibutyryl cyclic GMP did not affect basal, or carbachol stimulated secretion of α-amylase from rat pancreas. The nucleotide did not have a significant effect on⁴⁵Ca release from the pancreas nor did it alter the response to carbachol. The dibutyryl analogue of cyclic GMP did not duplicate or alter the inhibitory effect of carbachol on³H-leucine incorporation into pancreatic trichloroacetic acid-precipitable protein.

---

Résumé L'effet du dibutyryl GMPc sur la sécrétion d'α-amylase, l'efflux du⁴⁵Ca et la synthèse de nouvelles protéines dans le pancréas du rat, ont été étudiés. Le dibutyryl GMPc n'affecte ni la sécrétion d'enzyme basale ni celle stimulée par le carbachol. Le nucléotide n'a pas un effet significatif sur le relàchement du⁴⁵Ca du pancréas et n'altère pas la réponse du carbachol. L'analogue ne mime pas et ne change pas l'effet du carbachol sur l'incorporation du³H-leucine dans les protéines précipitées par l'acide trichloroacétique.

---

---

Supported by a grant from the Medical Research Council of Canada. The authors acknowledge the secretarial aide of MissC. Picard.     

Effect of vinblastine on pancreatic enzymes secretion induced by cyclic nucleotide derivatives.

Vinblastine did not affect the basal secretion of enzymes from the rat pancreas, but it potentiates the secretory response to dibutyryl cyclic AMP. This potentiation is confirmed by the observation of numerous pictures of exocytosis at the apical part of the acinar cell. Dibutyryl cyclic GMP by itself, or associated with vinblastine, failed to modify the spontaneous release of enzymes or the secretion induced by dibutyryl cyclic AMP.     

Effect of vinblastine on pancreatic enzymes secretion induced by cyclic nucleotide derivatives

Summary Vinblastine did not affect the basal secretion of enzymes from the rat pancreas, but it potentiates the secretory response to dibutyryl cyclic AMP. This potentiation is confirmed by the observation of numerous pictures of exocytosis at the apical part of the acinar cell. Dibutyryl cyclic GMP by itself, or associated with vinblastine, failed to modify the spontaneous release of enzymes or the secretion induced by dibutyryl cyclic AMP.This work was supported by the Institut National de la Santé et de la Recherche Médicale (France).     

Evidence against the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase activity in fat cells

Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue.     

Evidence against the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase activity in fat cells

Summary Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue.Acknowledgments. This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Université René Descartes (Paris V) and the École Pratique des Hautes-Etudes (3e Section).     

Effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylmethoxy coumarin) on cyclic nucleotide phosphodiesterases in human platelets

Summary The effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylmethoxy coumarin), an inhibitor of platelet aggregation, on cyclic nucleotide metabolism was investigated. AD6 inhibited selectively human platelet cyclic GMP phosphodiesterase, which was separated from cyclic AMP phosphodiesterase by DEAE-cellulose chromatography. Addition of AD6 to washed platelets increased cyclic GMP levels significantly in two minutes. These results could be useful in elucidating the action of AD6 on intact platelets.     

Effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylme tho xy coumarin) on cyclic nucleotide phosphodiesterases in human platelets

The effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylmeth oxy coumarin), an inhibitor of platelet aggregation, on cyclic nucleotide metabolism was investigated. AD6 inhibited selectively human platelet cyclic GMP phosphodiesterase, which was separated from cyclic AMP phosphodiesterase by DEAE-cellulose chromatography. Addition of AD6 to washed platelets increased cyclic GMP levels significantly in two minutes. These results could be useful in elucidating the action of AD6 on intact platelets.     

Protein synthesis and cyclic GMP content in rat cardiac muscle after swimming exercise

Rats were exercised for 6 h by swimming. Phenylalanine incorporation into myocardial proteins was increased when 2 h had elapsed after the termination of exercise. Cyclic GMP concentration did not change during the experiment, which indicates that cyclic GMP does not act directly as a trigger of myocardial protein synthesis in volume overload.     

Protein synthesis and cyclic GMP content in rat cardiac muscle after swimming exercise

Summary Rats were exercised for 6 h by swimming. Phenylalanine incorporation into myocardial proteins was increased when 2 h had elapsed after the termination of exercise. Cyclic GMP concentration did not change during the experiment, which indicates that cyclic GMP does not act directly as a trigger of myocardial protein synthesis in volume overload.     

Plasma cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate response to methacholine in man

Cholinergic agents are known to induce increases in tissue and plasma levels of cyclic GMP in experimental animals. We observed that i.m. injection of methacholine, a cholinergic agent, caused significant increases in plasma cyclic GMP and cyclic AMP in man.     

Increased urinary excretion of cyclic nucleotides in X-linked hypophosphatemic (Hyp) mice

Summary Hyp mice, a model for human X-linked hypophosphatemia, had elevated urinary cyclic AMP, cyclic GMP, and magnesium excretion compared to normal mice. The data suggest a renal origin of the urinary cyclic nucleotides. No significant differences in plasma cyclic AMP and cyclic GMP were observed between genotypes.This work was supported in part by research grants from The Kroc Foundation and the NIH, RR-09016.     

Rapid effects of insulin on cyclic GMP location in an intact protozoan.

We studied rapid changes in location of cyclic GMP in Tetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5-1 min). Later (1-5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes.     

Regulation of calcitonin release from the 6.23 rat C-cell line by cyclic nucleotide analogues and pharmacological mediators.

Calcitonin release from 6.23 rat medullary thyroid carcinoma C-cells was stimulated by dibutyryl cyclic AMP and inhibited by dibutyryl cyclic GMP in concentration dependent fashion. Histamine, isoproterenol, prostaglandin E2 and Bay K 8644 stimulated calcitonin release, while acetylcholine and serotonin had no significant effect on CT release.     

Increased urinary excretion of cyclic nucleotides in X-linked hypophosphatemic (Hyp) mice

Hyp mice, a model for human X-linked hypophosphatemia, had elevated urinary cyclic AMP, cyclic GMP, and magnesium excretion compared to normal mice. The data suggest a renal origin of the urinary cyclic nucleotides. No significant differences in plasma cyclic AMP and cyclic GMP were observed between genotypes.     

Zinc ions block the second but not the first phasic response to repetitive application of carbachol and histamine in guinea-pig taenia caeci

In the presence of Zn²⁺ (0.3 mM), carbachol (10^–6 M) or histamine (10^–5 M) induced the phasic response in guinea-pig taenia caeci while the tonic response was markedly inhibited. However, when the muscles were kept in Zn²⁺-containing medium following the first stimulation with either carbachol or histamine, neither application of carbachol nor of histamine elicited another phasic contraction. Caffeine (25 mM) did not induce contraction in the presence of Zn²⁺. After the washing out of caffeine in the presence of Zn²⁺, however, the muscle did then develop the phasic response on the application of carbachol or histamine. In conclusion, Zn²⁺ did not affect the carbachol or histamine-induced Ca²⁺ release from the storage sites. However, when Zn²⁺ was continuously present, Ca²⁺ was not supplied to the storage sites. Furthermore, carbachol and histamine mobilized a common cellular Ca²⁺ store, but they activated Ca²⁺ release channels different from the ones activated by caffeine in the Ca²⁺ storage sites.     

Rapid effects of insulin on cyclic GMP location in an intact protozoan

We studied rapid changes in location of cyclic GMP inTetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5–1 min). Later (1–5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes.     

Regulation of calcitonin release from the 6.23 rat C-cell line by cyclic nucleotide analogues and pharmacological mediators

Calcitonin release from 6.23 rat medullary thyroid carcinoma C-cells was stimulated by dibutyryl cyclic AMP and inhibited by dibutyryl cyclic GMP in concentration dependent fashion. Histamine, isoproterenol, prostaglandin E₂ and Bay K 8644 stimulated calcitonin release, while acetylcholine and serotonin had no significant effect on CT release.     

Circadian variation of adrenocortical cyclic nucleotides (cyclic AMP and cyclic GMP) in hypophysectomized rats

The existence of a circadian variation in the adrenocortical concentrations of cyclic AMP and cyclic GMP in male adult Wistar rats examined 10 days after hypophysectomy is demonstrated. The results suggest that the circadian variations of adrenocortical cyclic nucleotides observed previously in intact rats might not entirely depend upon pituitary corticotrophin.     

A negative inotropic effect of acetylcholine in the presence of several phosphodiesterase inhibitors

The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine (IBMX) reveal a negative inotropic effect of acetylcholine in cat ventricular heart muscle. This effect in unrelated to beta-adrenoceptor stimulation and possibly mediated by the accumulation of cyclic GMP.     

Inhibition of virus multiplication and alteration of cyclic AMP level in cell cultures by flavonoids

The inhibitory effect of four flavonoid compounds on virus multiplication and their influence on the intracellular cyclic AMP (cAMP) level were studied in cell cultures. Quercetin and quercitrin reduced the yields of Human (alpha) herpesvirus 1 (HSV-1) and Suid (alpha) herpesvirus 1 (pseudorabies virus), but hesperidin and rutin had no effect. Further, quercetin and quercitrin elevated the intracellular level of cAMP, whereas hesperidin and rutin did not alter the cAMP level. Both antiviral activity and cAMP-enhancing effect were dependent on the concentrations of the flavonoids, and these effects turned out to be parallel. This study suggests that a relation exists between the antiviral effect and the cAMP-enhancing activity of flavonoids.