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.     

Cell proliferation in the rat pituitary gland: a mechanism of control in prolactin cells.

We investigated the relationship between prolactin content and DNA replication in the anterior pituitary gland. Thymidine incorporation in pregnant rats is significantly lower than in virgin controls. This is accompanied by a decreased activity of DNA polymerase. Sulpiride administration to pregnant rats enhances thymidine incorporation to levels similar to virgin controls. The results indicate a negative feedback between prolactin content and DNA synthesis in the rat anterior pituitary gland.     

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.     

Cell proliferation in the rat pituitary gland: A mechanism of control in prolactin cells

Summary We investigated the relationship between prolactin content and DNA replication in the anterior pituitary gland. Thymidine incorporation in pregnant rats is significantly lower than in virgin controls. This is accompanied by a decreased activity of DNA polymerase. Sulpiride administration to pregnant rats enhances thymidine incorporation to levels similar to virgin controls. The results indicate a negative feedback between prolactin content and DNA synthesis in the rat anterior pituitary gland.We are grateful to Prof. Carlos J. Gómez for the opportunity to perform this work. These studies were supported by PLA-MIRH 99.178.1.78, by the Consejo Nacional de Investigaciones Científicas y Técnicas and by the Comisión Nacional de Energía Atómica (Argentina).     

Effect of in vivo pre-treatment with oestradiol and either GnRH,GnRH agonistic analog or GnRH antagonistic analog on GnRH-stimulated secretion of LH in vitro

Summary In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting effect of oestradiol became smaller with increasing rates of in vivo administration of GnRH or AG, but not with ANT. With respect to both depletion of the LH stores and suppression of the augmenting effect of oestradiol, AG ist about 20 times as potent as GnRH.     

Effect of in vivo pre-treatment with oestradiol and either GnRH, GnRH agonistic analog or GnRH antagonistic analog on GnRH-stimulated secretion of LH in vitro

In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting effect of oestradiol became smaller with increasing rates of in vivo administration of GnRH or AG, but not with ANT. With respect to both depletion of the LH stores and suppression of the augmenting effect of oestradiol, AG ist about 20 times as potent as GnRH.     

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

Summary Alrestatin at 25–1×10^–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.The author acknowledges the technical assistance of Miss C. Pilapil.     

4-Proline and 4-hydroxyproline analogs of arginine vasopressin: role of the proline substitution in the two beta-turns of vasopressin

[4-L-Proline]arginine vasopressin, [4-D-proline]arginine vasopressin, [4-hydroxyproline]arginine vasopressin and [4-proline, 7-hydroxyproline] arginine vasopressin were synthesized and found to have antidiuretic activities of 91 +/- 4, 1.7 +/- 0.2, 1.0 +/- 0.1 and 4.4 +/- 1.0 units/mg, respectively. None of these analogs exhibited a significant level of rat pressor activity. The observed activities of these and other analogs with substitutions at position 4 and/or 7 are discussed on the basis of hypotheses and data bearing on the solution conformation of vasopressins.     

Inhibition of rat liver transglutaminase by nucleotides

Summary Tissue-type transglutaminase (TGase) was purified from rat liver, and the effects of nucleotides on its activity were examined. The enzyme activity is inhibited by ATP in a concentration-dependent way, with complete inhibition by 3 mM ATP. Partially-purified TGase from human brain was inhibited by ATP in a manner similar to that observed with the rat liver enzyme. This suggests that the inhibition is a common phenomenon for tissue-type TGase in all species and tissues. The inhibition is reversible since full activity is restored by lowering the ATP concentration. CTP has a TGase-inhibitory potency equivalent to that of ATP, whereas GTP and UTP possess about 50% of the inhibitory activity of ATP. ADP inhibits TGase activity to the same extent as ATP, but AMP causes much less inhibition, and there is no inhibition by adenosine or adenine. The inhibition by ATP is insensitive to ionic strength and is non-competitive with the substrate putrescine. Since ATP levels in cells are of mM order, these results suggest that TGase activity is controlled by ATP in vivo.     

Inhibition of rat liver transglutaminase by nucleotides.

Tissue-type transglutaminase (TGase) was purified from rat liver, and the effects of nucleotides on its activity were examined. The enzyme activity is inhibited by ATP in a concentration-dependent way, with complete inhibition by 3 mM ATP. Partially-purified TGase from human brain was inhibited by ATP in a manner similar to that observed with the rat liver enzyme. This suggests that the inhibition is a common phenomenon for tissue-type TGase in all species and tissues. The inhibition is reversible since full activity is restored by lowering the ATP concentration. CTP has a TGase-inhibitory potency equivalent to that of ATP, whereas GTP and UTP possess about 50% of the inhibitory activity of ATP. ADP inhibits TGase activity to the same extent as ATP, but AMP causes much less inhibition, and there is no inhibition by adenosine or adenine. The inhibition by ATP is insensitive to ionic strength and is non-competitive with the substrate putrescine. Since ATP levels in cells are of mM order, these results suggest that TGase activity is controlled by ATP in vivo.     

Differences in luteinizing hormone release stimulated in rat anterior pituitary cells by leukotriene C4 and by gonadotropin-releasing hormone in vitro

Continuous administration of leukotriene C4 (LTC4, 10(-10) M) to superfused rat anterior pituitary cells increased LH release for 40 min only, whereas in a parallel experiment gonadotropin-releasing hormone (GnRH, 10(-9) M) evoked a continuous increase in hormone secretion. In contrast to GnRH, LTC4 did not desensitize rat anterior pituitary cells. The secretory action resulting from the administration of LTC4 (10(-10) M) was abolished for 40 min after previous stimulation. The results documented the dual action of LTC4 on LH exocytosis.     

Dipeptidyl aminopeptidase in neonatal rat brain regions

Summary Changes in the activity of dipeptidyl aminopeptidase in rat pituitary gland and various brain regions were examined at 3, 5 and 20 weeks of age. The enzyme activity per g tissue wet weight in pituitary gland was the highest of all tissues studied. Subcellular distribution of the activity was also studied. The highest enzyme activity was found in a crude mitochondrial fraction including synaptosomes.     

Oxytocin analogs effective as noncompetitive inhibitors in uterotonic test

Summary Deamino-1-carba-oxytocin analogs with a chemically reactive group in position 4 were demonstrated to act as noncompetitive oxytocin inhibitors in the assay on isolated rat uterus.     

Changes of X-prolyl dipeptidyl-aminopeptidase activity in developing rat brain.

We found X-prolyl dipeptidyl-aminopeptidase activity in rat brain and examined the developmental changes at various ages. The total enzyme activity per brain increased until 4 weeks of age, and then decreased during maturation. Specific activity in young rat brain was higher than that in adult rat brain. The properties of the brain enzyme were different from those of pituitary and other tissues.     

Changes of X-prolyl dipeptidyl-aminopeptidase activity in developing rat brain

Summary We found X-prolyl dipeptidyl-aminopeptidase activity in rat brain and examined the developmental changes at various ages. The total enzyme activity per brain increased until 4 weeks of age, and then decreased during maturation. Specific activity in young rat brain was higher than that in adult rat brain. The properties of the brain enzyme were different from those of pituitary and other tissues.     

Decidua and the control of corpus luteum function, follicular development and pituitary LHRH-responsiveness in pseudopregnant and pregnant rats

The mid-pregnancy rescue of corpora lutea can be mimicked in the pseudopregnant rat by induction of decidual tissue in the uterus: in such rats, around day 10, there is neither luteolysis, nor resumption of follicle-development or increase of the pituitary responsiveness to LHRH. The results suggest that the mid-pregnancy rescue of corpora lutea is caused by a maternal factor.     

Decidua and the control of corpus luteum function,follicular development and pituitary LHRH-responsiveness in pseudopregnant and pregnant rats

Summary The mid-pregnancy rescue of corpora lutea can be mimicked in the pseudopregnant rat by induction of decidual tissue in the uterus: in such rats, around day 10, there is neither luteolysis, nor resumption of follicle-development or increase of the pituitary responsiveness to LHRH. The results suggest that the mid-pregnancy rescue of corpora lutea is caused by a maternal factor.12 February 1987     

Pituitary-testicular relationships in the rat embryo]

LH given to the Rat embryo at the time of hypophysectomy by decapitation (18 days of intrauterine life) will prevent the drop in androgen synthesis which normally ensues. This is regarded as definite proof that androgen synthesis is under pituitary control in the rat embryo at late gestational stages. On the other hand, the decrease in androgen synthesis following testosterone injection to the pregnant female points to the fact that there is a negative feedback of testosterone on pituitary LH secretion.     

Effects of thyroidectomy and thyroxine replacement on the responsiveness of the anterior pituitaries from male rats to thyrotropin-releasing hormone in vitro

Summary Thyroidectomy decreased prolactin concentrations in the anterior pituitary (AP) and serum of the male rat. The amount of basal and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin by AP in vitro was lower in thyroidectomized (Tx) rats than in sham Tx rats. These results suggest that the inhibitory effects of thyroidectomy on pituitary and serum prolactin in male rats are mediated in part by the reduction of the production and spontaneous release of prolactin and the responsiveness of prolactin to TRH.     

Antidiuretic activities of substance P and its analogs

Summary Substance P (SP) and analogs, including 5 nucleoside (ARA or HRA)-peptides, were examined for antidiuretic activity in ethanolized rats. The activity was potent in the analogs embodying the C-terminal hexapeptide, weak in the nucleoside-pentapeptide, and negligible in the nucleoside-tetrapeptide. In addition, the activity was increased by acylation of the hexapeptide. The antidiuretic potencies were also compared with the hypotensive potencies.This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan, and by a grant from the Imanaga Foundation, Nagoya, Japan.