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.     

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

Dibutyryl cyclic GMP did not affect basal, or carbachol stimulated secretion of alpha-amylase from rat pancreas. The nucleotide did not have a significant effect on 45Ca 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 on 3H-leucine incorporation into pancreatic trichloroacetic acid-precipitable protein.     

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).     

Cyclic AMP is a likely mediator of ovulation in the tsetse fly.

Ovulation in tsetse flies is normally induced by mating, but virgins can be stimulated to ovulate with an injection of dibutyryl cyclic AMP, cholera toxin (a cyclic AMP generator), or aminophylline (a phosphodiesterase inhibitor). Thus, elevation of cyclic AMP is a likely link in the events leading to ovulation.     

Cyclic AMP is a likely mediator of ovulation in the tsetse fly

Summary Ovulation in tsetse flies is normally induced by mating, but virgins can be stimulated to ovulate with an injection of dibutyryl cyclic AMP, cholera toxin (a cyclic AMP generator), or aminophylline (a phosphodiesterase inhibitor). Thus, elevation of cyclic AMP is a likely link in the events leading to ovulation.We thank J. de Wilde and W.A. Foster for helpful comments. D.L.D.'s research visit to ICIPE was supported by a grant from the Mid-West Universities Consortium for International Activities.     

Stimulation of pyruvate carboxylation by gastric secretagogues

Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.     

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.

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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.

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

Stimulation of pyruvate carboxylation by gastric secretagogues

Summary Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.This investigation was supported by Consejo de Desarrollo Científico y Humanístico de la Universidad del Zulia, and by CONICIT Grant S1-0455.     

Effects of dibutyryl cyclic AMP on cultured brain cells from chick embryos of different ages

Summary The effect of dibutyryl cyclic AMP on cultivated astroblasts from 8-, 12- and 15-day-old chick embryo brain has been studied. The results show that these cells must have reached some degree of maturation in ovo to become morphologically differentiated by the cyclic nucleotide.     

Effects of dibutyryl cyclic AMP on cultured brain cells from chick embryos of different ages.

The effect of dibutyryl cyclic AMP on cultivated astroblasts from 8-, 12- and 15-day-old chick embryo brain has been studied. The results show that these cells must have reached some degree of maturation in ovo to become morphologically differentiated by the cyclic nucleotide.     

Effects of TSH and cyclic AMP on the human thyroid cells cultured in a chemically defined medium

Summary In a serum-free, chemically defined medium human thyroid cells elongated remarkably and resembled fibroblastic cells. They retained the cyclic AMP response to TSH and the supplement of medium with TSH or dibutyryl cyclic AMP permitted the preservation of epithelial nature by the cells. Cyclic AMP of the cells of epithelial nature was higher than those of fibroblastic appearance.     

Effects of TSH and cyclic AMP on the human thyroid cells cultured in a chemically defined medium.

In a serum-free, chemically defined medium human thyroid cells elongated remarkably and resembled fibroblastic cells. They retained the cyclic AMP response to TSH and the supplement of medium with TSH or dibutyryl cyclic AMP permitted the preservation of epithelial nature by the cells. Cyclic AMP of the cells of epithelial nature was higher than those of fibroblastic appearance.     

Effect of hormones and cyclic AMP on γ-glutamyltranspeptidase activity of rat mammary gland explants

Summary -Glutamyl transpeptidase activity was assayed in midpregnant rat mammary gland explants at 14, 22 and 38 h, in the presence and absence of insulin, prolactin and corticosterone. With these 3 hormones the explants attained the characteristics of a secretory gland after 22 h of tissue culture, at which time the enzyme exhibited its maximal activity. The addition of dibutyryl cyclic AMP in the presence of the 3 hormones produced a significant increase in enzyme activity, which was maximal with a 1 mM concentration of the cyclic nucleotide. A similar effect was observed when theophylline or theophylline plus dibutyryl cyclic AMP were added to the culture medium.This work was supported by grant B1138-8333 from the Departamento de Desarrollo de la Investigación, Universidad de Chile.     

Studies on the activity of phorbol myrystate acetate on the human polymorphonuclear leukocytes.

Phorbol myrystate acetate (PMA) activates nitroblue tetrazolium reduction in human polymorphs. The activation is inhibited by dibutyryl cyclic AMP, theophylline and phenylbutazone, but is not influenced by hydrocortisone in vitro, nor is it inhibited by leukocytes from patients treated with prednisone. Peptide analogues of Tuftsin also had no effect on this stimulatory activity. We conclude that the action of PMA on the nitroblue tetrazolium reduction is mediated through cyclic nucleotides.     

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.     

Studies on the activity of phorbol myrystate acetate on the human polymorphonuclear leukocytes

Summary Phorbol myrystate acetate (PMA) activates nitroblue tetrazolium reduction in human polymorphs. The activation is inhibited by dibutyryl cyclic AMP, theophylline and phenylbutazone, but is not influenced by hydrocortisone in vitro, nor is it inhibited by leukocytes from patients treated with prednisone. Peptide analogues of Tuftsin also had no effect on this stimulatory activity. We conclude that the action of PMA on the nitroblue tetrazolium reduction is mediated through cyclic nucleotides.     

Antithyroid effect of a food or drug preservative: 4-hydroxybenzoic acid methyl ester

Summary 4-hydroxybenzoic acid methyl ester (methylparaben) inhibits organification of iodide by isolated hog thyroid cells. The concentration which produces a 50% inhibition was about 2.0×10^–4M. A similar inhibition was observed in nonstimulated and TSH- or dibutyryl cyclic AMP-stimulated cells. Neither iodide uptake nor cyclic AMP generation were altered by methylparaben.     

Effect of dibutyryl cyclic AMP on cerebral energy charge and electrocorticographic activity in rats under asphyxic hypoxia]

In Rats anesthetized with pentobarbital and submitted to brief asphyxic episodes, intracerebroventricular administration of dibutyryl cyclic AMP inhibits the decrease of energy charge, delays the disappearance of electrocorticographic activity (E Co G) and shortens the recovery time of E Co G.     

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).