ABSTRACT
Recent investigations have demonstrated a modulatory action of glucagon on shivering via the central nervous system in ducklings. Such an action could be mediated by glucagon receptors that have been recently detected in several brain areas involved in the central control of the involuntary motricity in this avian species. The present study using des-His1 (Glu9) glucagon amide, was performed to investigate the central mechanisms of glucagon on shivering. This glucagon analog was found to be an antagonist of glucagon devoid of adenylate cyclase activity (GR2) by triggering the breakdown of inositol phosphate (GR1) in mammals hepatocytes. The intracerebroventricular administration of des-His1 (Glu9) glucagon amide or glucagon induced a marked inhibition of shivering in ducklings exposed to cold. It seems likely that GR1 receptors contribute to decreased shivering in ducklings exposed to cold. Central glucagon or des-His1 (Glu9) glucagon amide were devoid of thermogenic effect at thermoneutrality.
Subject(s)
Body Temperature Regulation/physiology , Cerebral Ventricles/physiology , Ducks/physiology , Glucagon/analogs & derivatives , Glucagon/pharmacology , Hormone Antagonists/pharmacology , Animals , Body Temperature Regulation/drug effects , Calorimetry, Indirect , Cerebral Ventricles/drug effects , Cold Temperature , Electromyography/drug effects , Glucagon/administration & dosage , Hormone Antagonists/administration & dosage , Injections, Intraventricular , Male , ShiveringABSTRACT
Glucagon has marked thermogenic and lipolytic effects in birds but could also be involved in the central modulation of neural activity on the basis of the recently discovered glucagon receptors in several areas of the brain in ducklings. The aim of this work was to investigate the possible role of these receptors in the modulation of thermogenic processes. Glucagon was infused into the lateral ventricle of the brain in ducklings after an acute cold exposure (4 degrees C, 2 h) or at thermoneutrality (25 degrees C). Electromyographic (EMG) data were simultaneously recorded with electrodes implanted in the gastrocnemius muscle. Glucagon (10(-4) M) was infused at a rate of 8 microliters/min. When acutely exposed to cold, ducklings increased their metabolic rate by shivering thermogenesis. A significant decrease in shivering activity was elicited after 5 min of glucagon infusion. After 16 +/- 2 min of glucagon infusion, shivering was completely inhibited, corresponding to a total dose of 36 +/- 4 micrograms/kg. The suppression of shivering was accompanied by a diminution of metabolic rate (5.3 +/- 0.3 vs. 8.5 +/- 0.2 W/kg, P < 0.05). The values of metabolic rate obtained at 4 degrees C after glucagon infusion were not significantly different from those measured at 25 degrees C before glucagon infusion (6.4 +/- 0.3 W/kg, P > 0.05). The infusion of the same dose of glucagon did not induce any change in EMG activity and resting metabolic rate at 25 degrees C. These findings suggest that glucagon infused into the brain has no thermogenic effect but could be involved in the central control of somatic motricity. Although the origin and the mechanisms of action of the endogenous peptide still remain unknown, glucagon might have a role in the development of non shivering thermogenesis during prolonged cold exposure via an inhibition of shivering in birds.
Subject(s)
Body Temperature Regulation/drug effects , Glucagon/pharmacology , Muscle, Skeletal/drug effects , Shivering/drug effects , Animals , Electromyography , Injections, Spinal , Muscle, Skeletal/physiology , Temperature , Time FactorsABSTRACT
The discovery of glucagon biosynthesis and receptors within mammalian brain has led one to suspect a neurotransmitter role for glucagon. In order to address this hypothesis in birds, we investigated the existence of glucagon receptors in duck brain by radioligand binding on fresh tissue sections and radioautography. Specific high-affinity [125I]glucagon binding sites similar to those in the liver were demonstrated in the avian brain. Mapping of these putative glucagon receptors revealed a discrete distributional pattern. Most of the [125I]glucagon binding capacity in duck brain is concentrated within the telencephalon, mainly in components of motor and limbic systems. Specific labeling densities were associated with avian equivalents of the mammalian pyramidal system (hyperstriatum accessorium; archistriatum intermedium and tractus occipitomesencephalicus) and extrapyramidal system (paleostriatum augmentatum, paleostriatum primitivum and lobus parolfactorius), as well as several limbic structures (hippocampal formation, nucleus taeniae and the caudal part of the archistriatum). Few glucagon-reactive foci were detected in the diencephalon (the nucleus dorsomedialis of hypothalamus, the two circumventricular organs, organum vasculosum of the lamina terminalis and median eminence and the nucleus habenularis medialis). These findings suggest that glucagon might be involved in the central control of somatic motricity and basic behaviors and point therefore to glucagon as a new neuroactive messenger in avian brain. The extensive difference between the distribution of glucagon binding sites observed in duck brain and that previously reported in rat brain suggests that glucagon does not subserve the same physiological role(s) in avian and mammalian brains.