ABSTRACT
Protein restriction impairs the salivary flow rate and composition in human and rats. The aim of the present work was to establish the effect of low protein (casein 5%) and protein free (casein 0%) isocaloric diets on sympathetic activity and salivary evoked secretion in the submandibular gland (SMG) of the rat. After 21 days, rats fed casein 0% presented: (a) a significant shift to the left of the dose-response curves (DRC) to the autonomic agonists-norepinephrine (NE), methoxamine, isoproterenol (ISO) and methacholine; (b) increased food consumption (p<0.001); (c) decreased body (p<0.001) and SMG (p<0.001) weights maintaining SMG/body (w/w) relation; (d) enhanced submandibular alpha1-adrenoceptor number without changes in the apparent dissociation constant (Kd); (e) increased submandibular NE content (p<0.05) and phosphoinositoside hydrolysis (p<0.001); (f) decreased submandibular tyrosine hydroxylase activity (TH) (p<0.01). Casein 5% feeding increased food consumption (p<0.01) and reduced body weight (p<0.05). This protein restriction increased metacholine-evoked salivation, but it altered neither submandibular sympathetic activity nor sympathetic-induced salivary secretion as compared to the Control group (C) fed a similar diet containing 25.5% protein. Present results suggest that in the adult rat, a protein free diet during 21 days lowers SMG sympathetic and cholinergic activity leading to supersensitivity as revealed by up-regulation of alpha1-adrenergic receptor number and increased autonomic-evoked salivation.
Subject(s)
Caseins/administration & dosage , Diet, Protein-Restricted , Protein-Energy Malnutrition/metabolism , Salivation/drug effects , Submandibular Gland/metabolism , Sympathetic Nervous System/physiology , Adrenergic alpha-Agonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Animals , Biomarkers/analysis , Caseins/metabolism , Cholinergic Agonists/pharmacology , Isoproterenol/pharmacology , Male , Methacholine Chloride/pharmacology , Methoxamine/pharmacology , Models, Animal , Phosphatidylinositols/metabolism , Random Allocation , Rats , Rats, Wistar , Submandibular Gland/drug effects , Sympathetic Nervous System/drug effects , Tyrosine 3-Monooxygenase/analysis , Tyrosine 3-Monooxygenase/metabolismABSTRACT
Neurons from the superior cervical ganglia (SCG) innervate the submandibular gland and release noradrenaline during the dark phase of the daily photoperiod. Since in the pineal, another structure innervated by sympathetic neurons, nocturnal activation of the SCG is associated with beta-adrenergic sub- and super-sensitivity rhythms, the possible existence of similar phenomena in the rat submandibular gland was assessed. Wistar female rats, kept on a 14:10 light/dark cycle (light from 06:00 to 20:00 h), were sacrificed at 09:00, 14:00, 20:00, 24:00 and 04:00 h. beta-Adrenoceptors were studied by 3H-dihydroalprenolol binding to membrane preparations. The equilibrium dissociation constant (Kd) did not change as a function of time while significant daily variations in maximal binding values (Bmax) were observed with a peak at 20:00 h. Changes in Bmax correlated with a high response of adenylate cyclase to isoproterenol. In addition, when the response in salivary flow to isoproterenol was measured. a shift to the left (about 1 logarithmic unit) in dose-response curves was observed at 19:00-20:00 has compared to 08:00-09:00 h. These daily variations in isoproterenol responsiveness seem not to depend on the pattern of eating since a 24-h starvation or a nocturnal starvation for 16-18 days did not abolish the morning-evening differences in the salivary flow response to isoproterenol. Rather, the results suggest that the daily variations in isoproterenol response correlate with beta-adrenergic super- and sub-sensitivity phenomena associated with the circadian release of noradrenaline from SCG neurons.
Subject(s)
Circadian Rhythm/physiology , Receptors, Adrenergic, beta/metabolism , Submandibular Gland/innervation , Submandibular Gland/metabolism , Adenylyl Cyclases/metabolism , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Antagonists/metabolism , Adrenergic beta-Antagonists/pharmacology , Animals , Dihydroalprenolol/metabolism , Dihydroalprenolol/pharmacology , Feeding Behavior/physiology , Female , Isoproterenol/pharmacology , Rats , Rats, Wistar , Saliva/metabolism , Superior Cervical Ganglion/physiology , TritiumABSTRACT
The lower and upper incisors of female rats were repeatedly reduced every 48 hr for 21 days. A marked enlargement of the submandibular glands was observed at the end of this period. One day after the final reduction, dose dependent curves to phenylephrine and isoproterenol were obtained in relation to salivary flow rates. Secretory responses, expressed as mg/gland, showed that the dose response curve to the alpha1-adrenomimetic drug was not modified by treatment while that for isoproterenol was shifted to the right of the control. When the responses were expressed as microg of saliva/mg of wet tissue, the dose-response curve to both agonists was shifted to the right in the incisor-reduced group. (Activation of alpha2-adrenergic receptors by clonidine did not inhibit the responses to phenylephrine in the incisor-reduced rats.) Radioligand binding assays of alpha1-, beta- and alpha2-receptors did not show differences between control and experimental glands in terms of densities (Bmax) or affinities (Kd). The lack of correlation between the decrease in alpha2- and beta-mediated responses and the radioligand bindings suggests that postreceptor mechanisms are involved in the diminished secretory responses of the rat submandibular gland after periodic reduction or amputation of incisors.
Subject(s)
Incisor/physiology , Receptors, Adrenergic/physiology , Submandibular Gland/metabolism , Adrenergic Agonists/pharmacology , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Incisor/surgery , Mandible , Maxilla , Periodicity , Radioligand Assay , Rats , Rats, Wistar , Receptors, Adrenergic/drug effects , Submandibular Gland/drug effects , Submandibular Gland Diseases/physiopathology , Time FactorsABSTRACT
Female Wistar rats were placed for 3 weeks in a simulated chamber evacuated by a vacuum pump and maintained at 40.5 kPa (7100 m). Dose-response curves were obtained through the sequential injection, via the femoral vein, of increasing doses of methacholine, methoxamine, isoprenaline and substance P. The secretory activity in the parotid gland after exposure to chronic hypoxia was significantly decreased for all agonists studied, and the submaxillary gland showed the same behaviour except in relation to isoprenaline, which did not show a significant difference compared to controls. These data suggest that changes in the number or sensitivity of autonomic receptors and/or alterations in the intracellular signals caused by hypoxia may be involved in the reduction in salivary secretory responses.
Subject(s)
Hypoxia/complications , Saliva/metabolism , Salivary Glands/metabolism , Xerostomia/etiology , Animals , Barotrauma/complications , Chronic Disease , Female , Isoproterenol/pharmacology , Methacholine Chloride/pharmacology , Methoxamine/pharmacology , Parotid Gland/metabolism , Rats , Rats, Wistar , Salivary Glands/drug effects , Secretory Rate , Stimulation, Chemical , Submandibular Gland/metabolism , Substance P/pharmacologyABSTRACT
The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. (alpha-1,4-glucan-4-glucanohydrolase) in parotid gland of 25 day old rats was studied under different experimental conditions (fast, reversed photoperiod, constant light or darkness and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of rats fasted or exposed for 7 days to constant darkness did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod and it disappeared in animals submitted to constant light or darkness for 15 days or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm persisted, with minor changes in the acrophase, in parotids of rats kept during their gestation and post-natal life in constant light or darkness. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, under autonomous nervous system control and maternal coordination. This model appears to be useful in the study of sympathetic nervous system control of target organs and circadian rhythms in general.
Subject(s)
Parotid Gland/enzymology , alpha-Amylases/metabolism , Age Factors , Animals , Circadian Rhythm , Fasting , Light , Male , Methyltyrosines/pharmacology , Rats , Rats, Inbred Strains , Regression Analysis , Reserpine/pharmacology , Sympathetic Nervous System/physiology , alpha-MethyltyrosineABSTRACT
The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. (alpha-1,4-glucan-4-glucanohydrolase) in parotid gland of 25 day old rats was studied under different experimental conditions (fast, reversed photoperiod, constant light or darkness and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of rats fasted or exposed for 7 days to constant darkness did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod and it disappeared in animals submitted to constant light or darkness for 15 days or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm persisted, with minor changes in the acrophase, in parotids of rats kept during their gestation and post-natal life in constant light or darkness. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, under autonomous nervous system control and maternal coordination. This model appears to be useful in the study of sympathetic nervous system control of target organs and circadian rhythms in general.
ABSTRACT
The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. (alpha-1,4-glucan-4-glucanohydrolase) in parotid gland of 25 day old rats was studied under different experimental conditions (fast, reversed photoperiod, constant light or darkness and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of rats fasted or exposed for 7 days to constant darkness did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod and it disappeared in animals submitted to constant light or darkness for 15 days or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm persisted, with minor changes in the acrophase, in parotids of rats kept during their gestation and post-natal life in constant light or darkness. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, under autonomous nervous system control and maternal coordination. This model appears to be useful in the study of sympathetic nervous system control of target organs and circadian rhythms in general.
ABSTRACT
The effects of continuous light on ultrastructural organization and sympathetic secretory responses of the rat parotid gland are reported. After 50 days of continuous light exposure, the fine structure of the parotid gland exhibited features of enhanced secretory activity as judged by the striking development of rough endoplasmic reticulum and Golgi complexes, the depletion of secretory granules and the increased turnover of secretory cells. The secretory responses of parotid gland to isoproterenol revealed that continuous light induced a 30% increase in amylase release. This secretory hyperactivity appears to be related to a postsynaptic supersensitivity of sympathetic fibers of the autonomic nervous system.
Subject(s)
Light , Parotid Gland/ultrastructure , Amylases/metabolism , Animals , Cytoplasmic Granules/ultrastructure , Endoplasmic Reticulum/ultrastructure , Golgi Apparatus/ultrastructure , Isoproterenol/pharmacology , Male , Microscopy, Electron , Parotid Gland/metabolism , Rats , Rats, Inbred Strains , Time FactorsABSTRACT
The effects of sub-chronic cadmium (Cd) administration on the structure and subsequent secretory responses of the submaxillary and parotid glands to sialagogues were investigated. Female Wistar rats were injected subcutaneously with cadmium chloride (3.0 mg/kg body weight), 4 times a week for 2, 3 or 4 weeks. Functional and histopathological studies were done 3 days after the last injection. Dose-response curves for norepinephrine and methacholine were obtained. After 2 weeks of Cd administration significant changes in the secretory response to these sialogogues were observed. The dose-response curves after pretreatment with Cd for 3 weeks were also shifted to the right, but the response showed recovery when compared with that of 2-week treated animals. Parotid amylase concentration was also diminished by Cd. Treated rats had reduced acinar diameters, and an increase in acinar cell nuclei per field in both the submaxillary and parotid glands. Thus sub-chronic administration of ionized Cd produces morphological and functional changes in rat salivary glands. Moreover, the extent of tubular and acinar damage matches the degree of gland dysfunction as judged by the diminution of secretory responses to sialagogues.