Comparison of diurnal and nocturnal rates of 5-hydroxytryptamine turnover in the rat mediobasal hypothalamus

Summary Rates of 5-hydroxytryptamine (5-HT) turnover in the mediobasal hypothalamus of male rats were estimated using pharmacological methods during the daytime and at night. Concentrations of 5-HT in this hypothalamic area were higher nocturnally than diurnally; this was apparently due to increased 5-HT synthesis and decreased 5-HT catabolism at night.Supported by NIH grant RR07187 (TSK) and NIH grant HD10202 (Neuroendocrine Core).     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

Summary The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

Influence of diet on plasma tryptophan and brain serotonin levels in mice

Summary Groups of mice were maintained for up to 78 weeks on tryptophan restricted, protein restricted and control diets. Plasma tryptophan levels were significantly reduced by both forms of dietary restriction. Brain serotonin levels were significantly reduced only in mice on the tryptophan restricted diet, but not for mice on the protein restricted diet. The protein-restricted diet contains less of the large neutral amino acids which compete with tryptophan to enter the brain. It is known that protein restriction and tryptophan restriction extend lifespan. The results presented here suggest that extension of lifespan and lowering of brain serotonin are not related.     

Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain

Summary The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Dopamine-beta-hydroxylase activity in adrenal gland and spleen of rats after fasting and cold exposure

Summary Fasting (48 h) results in dopamine-beta-hydroxylase (DBH) release both in adrenal gland and spleen, suggestive of an increase in the activity of these organs. Cold exposure (48 h) produces a dissociation of the, sympathoadrenal response. When both stimuli are simultaneously employed, the DBH response suggests the preponderance of the response to fasting. Plasma DBH is decreased in all groups studied, this could be due to its half-life and the splenic DBH depletion.This work was supported by a grant of Fondo de Investigaciones Sanitarias de la Seguridad Social, No. 83/0905.     

Glutathione-related enzyme activities in pregnant rat liver

Summary The levels of GSH-related enzyme activities during pregnancy were determined. A significant increase in Selenium-dependent GSH peroxidase and GSH S-transferase E activity was observed. A concomitant increase in -glutamylcysteine synthetase was measured, which indicated an increased ability to synthesize the tripeptide.     

Inhibition of TSH-stimulated thyroid hormone release and potentiation of TRH-stimulated TSH release by indomethacin in perifusion systems of rat thyroids and pituitaries

Summary Using indomethacin (Ind), a prostaglandin, synthesis inhibitor, in vivo experiments in rats and in vitro experiments with perifusion systems of rat thyroids and pituitaries were conducted. After 35 days of intragastric infusion of Ind, serum TSH levels were markedly increased, the thyroid was swollen and, as a consequence, T₃ and T₄ levels were normal. The T₃ release from perifused rat thyroids under continuous stimulation with 10 mU/ml TSH was inhibited significantly (p<0.01) by 1.0×10^–6 M Ind. On the other hand, the TSH release from perifused rat pituitaries under TRH stimulation was enhanced conspicuously by Ind. It was concluded that Ind decelerated thyroid hormone release from the thyroid and accelerated TSH release from the pituitary in perifusion systems.     

The effect of cycloheximide on nuclear uH2A content

Summary The effect of intraperitonal cycloheximide administration on acid-soluble rat liver chromatin proteins has been investigated by electrophoresis in acetic acid-urea polyacrylamide gels. A nonhistone protein, which migrates between oxidized histone H3 and histone H1 has been found tobe increased in amount following cycloheximide treatment. This protein seems to be identical with semihistone protein H24 (uH2A). A possible relationship of uH2A to the inhibition of rRNA synthesis is discussed.This work was supported by the Turkish Scientific and Technical Research Council (TUBITAK) Project No. TAG 339     

Selective effects of gonadal steroids on the response of peripheral serotonin receptors

Summary The maximal contraction provoked by serotonin (5-HT) in isolated stomach strips of adult rats, a functional index for peripheral 5-HT receptors, was sexually differentiated, androgen-sensitive, and estrogen refractory. This is at variance with the reported sensitivity of central 5-HT receptors to estrogen.     

Stress by restraining potentiates morphine catalepsy in rats

Summary Restraint-induced stress potentiated morphine catalepsy in rats. This potentiation was partially antagonized by pharmacologic treatments decreasing central serotonin, acetylcholine, prostaglandins and by naloxone. Selective increase in central dopamine also inhibited the potentiation.Acknowledgments. SKB is an ECFMG Senior Faculty Fellow from the Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. Partial research support by the Dakota State Aerie Fraternal Order of Eagles is gratefully acknowledged.     

Fluid and protein clearance in the rat endometrium. Part II: Ultrastructural evidence for the presence of alternative,non-lymphatic clearance mechanisms in the rat endometrium

Summary In the rat endometrium, resident macrophages and exudate phagocytes ensure proteolysis by means of phagocytosis, macro-and micropinocytosis. Using exogenous tracer particles no ultrastructural evidence could be obtained for the occurrence of endometrial prelymphatics. It is suggested that the free tissue fluid may be drained via the fenestrated (probably venous) blood capillaries.Supported by a grant from the Nationaal Fonds voor Wetenschappelijk Onderzoek-Fonds voor Geneeskundig Wetenschappelijk Onderzoek (Belgium).     

Tumor-derived angiogenesis factors from rat Walker 256 carcinoma: an experimental investigation and review

Summary Angiogenesis, the process of developing a hemovascular network, is an essential feature of the growth of solid tumors, and is induced by factors secreted by tumor cells. Assay procedures suitable for the investigation of angiogenesis, and for the screening of angiogenesis factors during purification are reviewed; and a number of reports describing the purification of angiogenesis factors, primarily from the rat Walker 256 carcinoma as starting material, are discussed. Work from the authors' laboratory is also presented. Walker 256 cells grown in large-scale culture were the source of a reproducible and homogeneous source of angiogenic material. Factors secreted by these cells were isolated by a series of chromatographic steps. Ion exchange chromatography on carboxymethyl-Sephadex produced two active fractions, one of which was fractionated into several macromolecular species by lectin affinity and hydrophobic adsorption chromatography. The other gave a high mol.wt, active fraction that was resolved into a low mol.wt, active component and a non-angiogenic but possibly carrier molecule with a mol.wt of 140,000. While none of the angiogenic factors were identified chemically, the results demonstrate the existence of both high and low mol.wt tumor-secreted angiogenic substances, confirming the hypothesis for tumor-induced angiogenesis and predicting potential means to interfere with the process of tumor growth.This work was supported by funds from the Monsanto Company under Agreements with Harward University and from the U.S. Public Health Service, Contract No. N01-CB-43942. We are particularly indebted to Bernard S. Wildi and Monte C. Throdahl for their advice, cooperation, and encouragement. We also thank Dr Judah Folkman for the initial supply of male mouse submaxillary glands and rat Walker carcinoma conditioned medium, for help with the CAM assays, assays in the rabbit cornea, and many helpful discussions; and R. Bretton, A. Ehrlich, B. Evans, F. Fu, N. Hay and B. Tsokanis for excellent technical assistance.Author to whom correspondence should be addressed.     

The effect of castration,testosterone and estradiol on14C-serotonin metabolism by organ cultures of male rat pineal glands

Summary The pineal gland of the male rat does not appear to rely on prior conversion of testosterone to estradiol for the stimulant effect of testosterone on pineal melatonin and 5-methoxytryptophol synthesis.     

The role of phosphoenolpyruvate in insulin secretion: the effect of L-phenylalanine

Summary Incubation of rat islets with phenylalanine increased the tissue content of phosophoenolpyruvate, both in the presence and in the absence of glucose. At the same time, L-phenylalanine neither stimulated nor inhibited insulin release. It is unlikely that insulin secretion is tightly coupled to the availability of phosphoenolpyruvate in rat islets.     

Both thermal and nociceptive afferents influence the unit activity of the neurons in the corpus striatum

Summary Both thermal and nociceptive stimulation in the periphery were shown to influence the neuronal activity recorded in the striatal area. Both the thermal and nociceptive sensitivity of the striatal neurons were closely related.The authors are grateful to the Alexander von Humboldt-Stiftung (Bad Godesberg, Bonn, Federal Republic of Germany) for donations of the necessary equipment for the present study. The research reported here was supported by grants from the National Science Council (Taipei, Taiwan, Republic of China)     

Fluid and protein clearance in the rat endometrium. Part I: Ultrastructural proof of the absence of an intrinsic lymphatic system from the rat endometrium

Summary An integrated histological and ultrastructural study of the endometrial microcirculation in rats reveals that lymphatic capillaries are absent from the superficial uterine mucosa. Blood capillaries are fenestrated, and their basement membrane may be poorly developed.Supported by a grant from the Nationaal Fonds voor Wetenschappelijk Onderzoek-Fonds voor Geneeskundig Wetenschappelijk Onderzoek (Belgium).     

Methylation of hippocampal phosphatidylethanolamine and proteins during long-lasting potentiation

Summary Whereas the monomethylation of hippocampal phosphatidylethanolamine is decreased following the induction of long-lasting potentiation of the CA₁ population spike, carboxymethylation of proteins is unaffected.This work was supported by The University of British Columbia.     

Neural discharge can be modulated by carotid arterial injection of gastrin-17 in rat hypothalamic paraventricular nucleus

Neural discharge in the hypothalamic paraventricular nucleus (PVN) was examined after gastrin-17 injection into the carotid artery in anesthetized rats. Neural discharge was increased by gastrin-17 injection into the carotid artery close to the cranium, and the response due to the gastrin was dose-dependent. No discharge response was seen when gastrin was injected into the jugular vein. These results suggest that gastrin circulating in the arterial blood can penetrate the blood brain barrier, and modulate neural PVN activity which is responsible for gastric acid secretion.     

Hypothalamic tyrosine hydroxylase activity,plasma gonadotropin and prolactin levels after aminooxyacetic acid in ovariectomized rats

Summary Plasma concentrations of gonadotropin, prolactin and hypothalamic tyrosine hydroxylase (TH) activity were measured in ovariectomized rats treated with aminooxyacetic acid (AOAA), a drug which elevates brain GABA levels. Hypothalamic TH activity was significantly increased with a significant decrease in prolactin (Prl) release. Plasma levels of gonadotropins were not modified by AOAA. These results support an inhibitory action of GABA on Prl release possibly mediated through hypothalamic dopamine.Supported by grants from Indian Council of Medical Research (ICMR), New Delhi. RIA kits for the estimation of LH, FSH and Prl were kindly supplied by Dr A.F. Parlow, NIAMDD-NIH, Bethesda, Maryland, USA. GNB is a UGC research fellow.     

Evidence for an activating effect of tabernathine on rat brain catechlomine synthesis and elimination

Summary Tabernanthine increased the synthesis and elimination of catecholamines (CA) in the striatum and the rest of the brain, but not in the hypothalamus. These data provide evidence that tabernanthine may activate CA turnover of some brain structures by acting at 2 steps of the metabolic pathway. The results are discussed in relation to a central stimulating action and a hypoxia antagonistic effect of this drug.Acknowledgments. Tabernanthine was generously provided by the Institut de Chimie des Substances Naturelles of the C.N.R.S., Gifsur-Yvette, by B. Poiteau, Dat-Xuong, H. P. Husson, Mme Ch. Kan-Fan and P. Potier.