ABSTRACT
OBJECTIVES: The aim of the present work was to study the effect of long-term cyclosporine (CSA) administration on norepinephrine (NE) metabolism and adrenergic-evoked secretion in the rat submandibular gland (SMG). METHODS: Dose-response curves to adrenergic agonists (methoxamine, isoproterenol, NE) were performed in control and CSA (10 and 30 mg/kg every 2 days for 1 month)-treated rats after SMG duct cannulation. In SMG tissue neuronal NE uptake, release, synthesis and endogenous content were determined. In addition phosphoinositide intracellular signaling was also investigated. RESULTS: CSA administration caused an increase in salivary secretion evoked by methoxamine (alpha-adrenergic agonist) and NE but failed to modify salivation evoked by beta-adrenergic stimulation (isoproterenol). Long-term CSA administration decreased NE release and synthesis whereas it enhanced the amine uptake and phosphoinositide hydrolysis in the SMG. CONCLUSIONS: The administration of CSA for 30 days induced salivary gland sensitization likely mediated by diminished adrenergic input. Present results suggest that the decreased sympathetic activity evoked by long-term CSA administration in the rat SMG may lead to sensitization of the gland supported by increased phosphoinositide hydrolysis and enhanced adrenergic-evoked salivation.
Subject(s)
Cyclosporine/pharmacology , Immunosuppressive Agents/pharmacology , Norepinephrine/metabolism , Salivation/drug effects , Submandibular Gland/drug effects , Sympathetic Fibers, Postganglionic/drug effects , Adrenergic alpha-Agonists/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Administration Schedule , Hydrolysis/drug effects , Male , Methoxamine/pharmacology , Norepinephrine/pharmacology , Phosphatidylinositols/metabolism , Rats , Rats, Wistar , Salivation/immunology , Submandibular Gland/innervation , Submandibular Gland/metabolism , Sympathetic Fibers, Postganglionic/immunology , Sympathetic Fibers, Postganglionic/metabolismSubject(s)
Dietary Proteins/administration & dosage , Erythropoietin/administration & dosage , Polycythemia/blood , Animals , Caseins/administration & dosage , Egg Yolk , Erythrocytes/metabolism , Female , Glutens/administration & dosage , Iron/blood , Male , Protein Deficiency/blood , Rats , Starvation , Zea maysABSTRACT
Radioiron uptake by erythrocytes, metabolic rate, erythropoietin formation during hypoxia and erythroid responsiveness to exogenous erythropoietin were determined in both starved and water deprived rats. The feed intake showed a marked and progressive reduction during water deprivation. The metabolic rates of rats deprived of either food of water declined progressively showing a 40% reduction 5d after water deprivation or starvation began. At this time, the 24 h red blood cells 59Fe incorporation was 85% lower in both starved and dehydrated rats than in normal rats. Plasma erythropoietin levels in response to hypoxia were approximately 50% decreased in both starved and dehydrated rats. Both polycythaemic starved and polycythaemic water deprived rats injected with human urinary erythropoietin showed a 75% decrease in 59Fe incorporation into erythrocytes when compared to control rats. It is suggested that depression of erythropoiesis during water deprivation in the rat depends on a reduced sensitivity to erythropoietin, possibly associated with decreased production of the hormone. Since water deprived rats drastically reduce feed intake it is suggested that secondary starvation is the principal cause of the decreased erythropoiesis induced in the rat by water deprivation.