Cellular changes of adrenal under the acute stress of O-chlorobenzylidene malononitrile (CS)

Summary This investigation describes histological and cytometrical changes of cortical and medullary tissue of adrenal in rats under the acute stress of O-chlorobenzylidene malononitrile (10 mg/kg and 20 mg/kg). It has been observed that after injection of CS, the adrenal gland showed histological changes both in the cortical and medullary region.The authors are thankful to Dr. P.K. Ramachandran, Director, Defence Research and Development Establishment, Gwalior, for his sustained interest and critical suggestions in the course of this study.     

Histological changes in thyroid of rat under the acute exposure of O-chloro-benzylidine malononitrile

Summary This communication describes histological changes in the thyroid gland of rats under the acute stress of O-chlorobenzylidene malononitrile (CS) (10 mg/kg and 20 mg/kg). It has been observed that CS, when injected, causes histological changes in the thyroid of varying degrees, depending on the dose used.     

The corticotropin-releasing factor (CRF) family of peptides as local modulators of adrenal function

Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal (HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF₁) and 2 (CRF₂) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance between the local concentration of CRF ligands and the availability of their receptors. Received 19 December 2006; received after revision 20 February 2007; accepted 26 March 2007     

Metallothionein induction by cadmium and zinc in rat secretory organs

Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2-4.9 micrograms/g wet weight tissue while in the pancreas it was shown to be 15.2 micrograms/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Histochemische Untersuchungen über den Einfluss von Iproniazid (Marsilid) auf die durch Reserpin erzeugte Freisetzung von Adrenalin und Noradrenalin aus dem Nebennierenmark

Summary A single injection of 10 mg/kg reserpine causes marked decrease of catecholamine in the medulla of the adrenal gland of rats. Histochemically, this can be shown by the disappearance of chromaffinity and of the potassium iodate reaction. After pretreatment with 100 mg/kg of iproniazid, reserpine injection induces little or no decrease in the histochemical reactions of adrenalin and noradrenalin. In animals pretreated with equimolar doses of isoniazid, however, histochemical catecholamine reactions are well preserved in all cells of the adrenal medulla. These results suggest that monoamine oxidase plays a part in the reserpine-induced release of catecholamine.     

Metallothionein induction by cadmium and zinc in rat secretory organs

Summary Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2–4.9 g/g wet weight tissue while in the pancreas it was shown to be 15.2 g/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Influence of flupirtine, a novel nonopioid analgesic agent on somatosensory evoked potentials in rats.

The effect of flupirtine, a novel nonopioid analgesic, on somatosensory evoked potentials (SEP) was investigated in anesthetized rats. Primary somatosensory potentials were evoked in the cerebral cortex by stimulation of the skin of the whiskery part of the face. Flupirtine injected i.p. dose-dependently prolonged the latency and reduced the amplitude of SEP with ID50-values of 5.4 mg/kg (2.6-9.3 mg/kg) and 7.9 mg/kg (3.9-13.8 mg/kg), respectively. This effect of flupirtine (10 mg/kg, i.p.) on the latency and the amplitude of SEP, did not change when naloxone (1 mg/kg, i.p.) was given before flupirtine. The results indicate that the analgesic flupirtine decreases the primary somatosensory evoked potential by diminishing the excitability of cortical neurons. Opioid mechanisms are not involved.     

Increase in the oxygen available to the cerebral cortex after the administration of carbonic anhydrase inhibitors]

Oxygen tension (pO2) in cerebral cortex was measured by polarographic method in unanesthetized rabbits. Intravenous administration (25 mg/kg) of carbonic anhydrase inhibitors (acetazolamide, methazolamide, dichlorphenamide, sulthiame) induced an early important rise of cortical p O2, which is not dependent on increase of p O2 and p CO2 and decrease of pH in arterial blood. High dosage of acetazolamide (250 mg/kg) produced the same effect and did not suppress the increase of cortical p O2 under air-CO2 inhalation. This result suggests that CO2 might act specifically upon cerebral vessels.     

Influence of flupirtine,a novel nonopioid analgesic agent on somatosensory evoked potentials in rats

The effect of flupirtine, a novel nonopioid analgesic, on somatosensory evoked potentials (SEP) was investigated in anesthetized rats. Primary somatosensory potentials were evoked in the cerebral cortex by stimulation of the skin of the whiskery part of the face. Flupirtine injected i.p. dose-dependently prolonged the latency and reduced the amplitude of SEP with ID₅₀-values of 5.4 mg/kg (2.6–9.3 mg/kg) and 7.9 mg/kg (3.9–13.8 mg/kg), respectively. This effect of flupirtine (10 mg/kg, i.p.) on the latency and the amplitude of SEP, did not change when naloxone (1 mg/kg, i.p.) was given before flupirtine. The results indicate that the analgesic flupirtine decreases the primary somatosensory evoked potential by diminishing the excitability of cortical neurons. Opioid mechanisms are not involved.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat.

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4 degrees C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4 degrees C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4°C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4°C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.This work was supported by a grant from the National Aeronautics and Space Administration (NSG 2183 and NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811) and a grant from the Division of Research Resources (NIH grant RR 03020).     

Effet inhibiteur de la tétrabénazine sur l'influence corticosurrénalienne de la réserpine

Summary Reserpine provokes an intense and long-lasting (more than 20 h) stimulation of the adrenocortical activity of the rat. Tetrabenazin (50 mg/kg) also produces an adrenocortical stimulation which is, however, of a much shorter duration. The injection of tetrabenazin 1 h before the injection of reserpine (5 mg/kg) prevents the prolonged stimulating effect of reserpine on the adrenal cortex. This effect can be compared with the blocking effect of tetrabenazin, a short-acting central depressant with monoamine-liberator properties, against the prolonged central sedative influence of reserpine.     

Intravenous thyrotropin releasing hormone (TRH) enhances the excitatory actions of acetylcholine (ACh) on rat cortical neurons

Summary I. v. administered TRH (1.25-10 mg/kg) enhanced the excitatory actions of iontophoretically applied ACh on spontaneously active cerebral cortical neurons of pentobarbital-anaesthetized rats. These observations are consistent with the hypothesis of a cholinergic-link in the anti-anaesthetic actions of exogenously administered TRH.     

Adrenocorticotrophic hormone and cyclic adenosine monophosphate effect on mouse adrenal cortical cell membrane potential

Adrenocorticotrophic hormone (ACTH) and cyclic adenosine monophosphate (cAMP) both caused a rapid and transient depolarization of the resulting membrane potential of superfused rat adrenal cortical cells. The membrane depolarization to both secretagogues were very similar. The membrane potential changes occurred as early as 0.1 min and were dose dependent in both onset and extent of depolarization.     

Endocrine cells producing regulatory peptides

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Latent iron deficiency alters gamma-aminobutyric acid and glutamate metabolism in rat brain

A diet containing 18-20 mg iron/kg to young weaned rats for 8 weeks altered the metabolism of gamma-aminobutyric acid and glutamate in the central nervous system without affecting blood hemoglobin. Subsequent rehabilitation with 390 mg iron/kg diet for 2 weeks normalized these changes.     

Kinetic studies on soluble and membrane-bound dopamineβ-hydroxylase isolated from storage vesicles of heart and adrenal medulla of different species

Summary IdenticalK _m-values for soluble and membrane-bound dopamine -hydroxylase isolated from adrenal medullary vesicles of different species were obtained; the same holds true for both forms of the enzyme of heart vesicles.The excellent technical assistance of MissSabine Klemt is gratefully acknowledged.     

Latent iron deficiency alters gamma-aminobutyric acid and glutamate metabolism in rat brain

Summary A diet containing 18–20 mg iron/kg to young weaned rats for 8 weeks altered the metabolism of gamma-aminobutyric acid and glutamate in the central nervous system without affecting blood hemoglobin. Subsequent rehabilitation with 390 mg iron/kg diet for 2 weeks normalized these changes.     

Endorcine cells producing regulatory peptides

Summary Recent data on the immunologication of regulatory peptides and related propeptide sequences in endocrine cells and tumours of the gastrointestinal tract pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory beenrevised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptidesare the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, -MSH and CLIP (corticotropoin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenalin-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Adrenal responses to hypoxia and hypercapnia in the young calf

Summary Quantitative analysis of adrenal responses to moderate hypoxia and hypercapnia in the conscious calf shows that the sensitivity of the adrenal cortical response far exceeds that of the adrenal medulla.Acknowledgment. This work has been supported by grants from the Agricultural Research Council, the Medical Research Council and the Wellcome Trust. We are also indebted to Dr D. M. Burley (CIBA) for his continued support.