Inhibition of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary by alrestatin.

Alrestatin at 25-1 X 10(-4) M inhibited the accumulation of cyclic AMP induced by prostaglandin E2, but not theophylline, in the rat anterior pituitary in vitro. Somatostatin, at lower concentrations, inhibited both; maximal inhibition of the prostaglandin effect was greater with alrestatin. As cyclic AMP is considered to be a mediator in induced-hormonal release, it appears from the present findings that alrestatin may be of potential use in altering hormonal release.     

Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogues

Summary The PGE₂-induced cyclic AMP accumulation in the rat anterior pituitary in vitro is inhibited by [desamino¹]-, [desamino¹] [descarboxy¹⁴] and [d-Lys⁴]-somatostatin similarly to somatostatin, while the [descarboxy¹⁴]-somatostatin exhibits reduced activity; [d-Lys⁹]-somatostatin is ineffective at a higher concentration.The authors acknowledge the technical assistance ofG. Alexander. F. Bellini, D. Mangerel andJ. Rochon and thank Dr.G. Schilling and his associates for the analytical data.     

Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogues.

The PGE2-induced cyclic AMP accumulation in the rat anterior pituitary in vitro is inhibited by [desamino1]-[desamino1] [descarboxy14]- and [D-Lys4]-somatostatin similarly to somatostatin, while the [descarboxy14]-somatostatin exhibits reduced activity; [D-Lys9]-somatostatin is ineffective at a higher concentration.     

Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin

Summary Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E₂ in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastrointestinal activities reflecting duration of availability rather than receptor affinity.The author acknowledges the technical assistance of Mr L. Chamberland, Miss A. Colaviti and Miss C. Pilapil.     

Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin.

Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E2 in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastro-intestinal activities reflecting duration of availability rather than receptor affinity.     

Inhibition of LH-RH induced release of gonadotropins by substance P in cultured rat anterior pituitary cells]

Using anterior pituitary cells cultured for 7 days and then incubated for 4 hrs, substance P, an undecapeptide, inhibited the stimulatory effect of LH-RH on the release of LH-RH on the release of LH and FSH. This inhibitory effect, which was similar for both gonadotropins was only observed when the adenopituitary cells were put in culture at DI and Proestrus stages of the oestrous cycle. Furthermore substance P partly inhibited the basal release of FSH at DI and DII stages but did never affected that of LH.     

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.     

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

Summary 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 ofHuman (alpha) herpesvirus 1 (HSV-1) andSuid (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.     

Possible regulation of membrane-associated cyclic AMP phosphodiesterase in rat cerebral cortex by lipids

Summary Cyclic AMP phosphodiesterase (PDE) in membrane fraction from rat cerebral cortex was activated by Triton X-100, and treatment at alkaline pH and with phospholipase C. These results suggest that membrane PDE exists in a latent form and is influenced by microenvironmental changes within the membrane. Furthermore, the PDE, unlike soluble enzyme, is not influenced by a protein activator and Ca⁺⁺.     

Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro

Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analog, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.     

Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro

Summary Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analogs, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.Acknowledgments. Supported by SNSF grant No. 3.327.078. The authors express their gratitude to Miss G. Allenbach for her excellent technical assistance and to Mr F. Pillonel for drawing the graphs.     

Possible regulation of membrane-associated cyclic AMP phosphodiesterase in rat cerebral cortex by lipids.

Cyclic AMP phosphodiesterase (PDE) in membrane fraction from rat cerebral cortex was activated by Triton X-100, and treatment at alkaline pH and with phospholipase C. These results suggest that membrane PDE exists in a latent form and is influenced by microenvironmental changes within the membrane. Furthermore, the PDE, unlike soluble enzyme, is not influenced by a protein activator and Ca++.     

Pineal-related changes in cyclic AMP levels of rat medial basal hypothalamus

Summary Pinealectomy (Px) in adult male rats resulted in increased cyclic AMP accumulation by medial basal hypothalamic (MBH) explants 3 and 7 days after surgery. 24 h after superior cervical ganglionectomy (Gx) an augmented MBH cyclic AMP accumulation was observed. The effects of Px and Gx were additive, as revealed in animals subjected to Gx 3 days after Px.This study was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (N^o 6638) and from the Fundación Alberto J. Roemmers, Argentina.     

Hormone and forskolin-stimulated cyclic AMP accumulation in human lymphocytes: reliability of longitudinal time measurements

Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E1 significant reliability was observed only for male subjects.     

Hormone and forskolin-stimulated cyclic AMP accumulation in human lymphocytes: reliability of longitudinal time measurements

Summary Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E₁-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E₁ significant reliability was observed only for male subjects.Acknowledgment. This work was supported in part by the following organizations: Chief Scientist's Office, Israel Ministry of Health; Herman Goldman Foundation, New York; United Jewish Endowment Fund of Greater Washington-Pollinger Foundation.