Adenosine triphosphate--dependent calcium uptake by rat submaxillary gland microsomes.

Microsomes from rat submaxillary glands are able to take up calcium from the suspension media. Calcium uptake is greatly increased by the presence of ATP. This effect of ATP is not detected at 0 degrees C. ADP cannot replace ATP to potentiate calcium uptake. ATP-dependent calcium uptake is not observed in the absence of magnesium. ATP-dependent calcium uptake is enhanced by oxalate and, to a lesser degree, by inorganic phosphate. Total calcium per milligram of microsomal protein observed when tests were performed without oxalate closely parallels the amounts for skeletal and cardiac muscles reported by several authors. Calcium uptake in salivary gland microsomes is slower than in muscle microsomes. Speculations are considered about the role of ATP-dependent calcium uptake. It is suggested that a decrease in intracellular free calcium levels returns these cells to the resting state after secretion.

The role of the caudate-putamen nucleus in salivary secretion induced by L-DOPA.

Experiments were performed in rats of the Wistar strain anesthetized with alpha-chloralose (100 mg/kg). Electrolytic lesion of either components of the striopallidal complex (corpus striatum, globus pallidus or entopeduncular nucleus) reduced the sensory response to L-DOPA in the contralateral submaxillary glands. Damage to other neural structures, directly or indirectly related to the striopallidal system, left the salivary response unaffected. These structures were: substantia nigra, cerebral cortex, ventromedial and center median-parafascicular thalamic nuclei, nucleus accumbens and posterior hypothalamic areas, including the medial forebrain bundle and lateral habenular nucleus. However, lesions placed in H1-H2 fields of Forel and reticular formation, lateral to the periaqueductal gray, reduced the salivary response in the contralateral glands. This effect was similar to that observed in animals with lesions of the striopallidal complex. From this study, it is concluded that the striatum is the target area for the central effect of L-DOPA on salivary secretion, by activation of pathways descending through the fields of Forel and mesencephalic reticular formation to the contralateral lower brain stem.

Selective increase of alpha 1-adrenoceptors and muscarinic cholinergic receptors in rat cerebral cortex after chronic haloperidol.

The effect of chronic administration of haloperidol on alpha 1-, alpha 2-, and beta-adrenoceptors, cholinergic muscarinic, GABAA and benzodiazepine receptors in the cerebral cortex of the rat was investigated. Doses of 0.3 and 2 mg/kg of haloperidol during 7 days increased markedly the density of alpha 1-adrenoceptors without changes in affinity. The alpha 2- and beta-adrenoceptors were not modified after neuroleptic administration. The number of muscarinic receptors were also increased after haloperidol treatment (2 mg/kg/day). However, the GABAA and benzodiazepine binding sites remained unchanged. In the brainstem an increment in the alpha 1-, but not the beta-adrenoceptors was observed. The well known increase in the dopamine receptors in the striatum was confirmed. These observations demonstrate a multireceptor effect of haloperidol in the cerebral cortex.

Studies on the mechanisms of L-dopa-induced salivary secretion.

Systemic administration of L-dopa and dopamine elicited a marked and sustained secretory response in the rat's submaxillary glands. These effects were blocked by pretreatment with phentolamine plus propranolol. Acute unilateral sympathectomy (decentralization or denervation) reduced the response to L-dopa by about 41-48%. But it left unchanged the secretory response to dopamine. Chemical sympathectomy by hexamethonium caused a similar reduction (45%) in the secretory response to L-dopa while parasympathectomy was unable to modify the salivary secretion caused by L-dopa or dopamine. Pretreatment with haloperidol reduced the salivary secretion to L-dopa in normal animals (unoperated glands), while the response to dopamine was unaffected. On the other hand, haloperidol did not alter the salivary response to L-dopa in animals with surgical sympathectomy (denervation) as compared to the same animals treated with L-dopa alone. From this study we conclude that the salivary secretion induced by L-dopa is mediated by both central and peripheral mechanisms. Dopaminergic receptors may be involved in the central effect and alpha- and beta-receptors in the peripheral response.

Chronic haloperidol causes increase in salivary response and alpha 1-adrenoceptors in submandibular gland of the rat.

The effect of chronic haloperidol on the receptor-secretion coupling of the submandibular glands of the rat was studied. After injection of 2 mg/kg haloperidol daily for 7 days, the dose-response curve to L-noradrenaline was displaced to the left, with lowering of the threshold and enhancement of the maximal response. This was accompanied by a 73% increase in alpha 1-adrenoceptors in the glands. The effect was selective, since no changes were observed in alpha 2- and beta-adrenoceptors.

Kinetics of calcium metabolism in rat dentin and enamel.

The time course of the specific activity of 45Ca in the dentin and enamel of rat incisors and molars was followed after an intravenous injection of the radiotracer. It was then correlated with the specific activity of 45Ca in plasma to obtain the accretion rates on the dentin of molars and incisors. The exchangeable calcium pool sizes in the dentin and the enamel of the molar were also calculated.

Secretory effects of 6-hydroxydopamine in normal and denervated submaxillary glands of the rat.

Injection of 6-hydroxydopamine (6-OH-DA) elicited a marked and sustained secretory response of control and surgically sympathectomized submaxillary glands of rats. These responses were diminished by previous treatment with reserpine 0.1 mg/kg 48 and 24 h before the experiment and almost abolished by 5 mg/kg reserpine 6 h before the administration of 6-OH-DA. The responses to 6-OH-DA were potentiated in control glands by previous preganglionic denervation of either the parasympathetic or sympathetic nerves of the gland. Development of postjunctional supersensitivity in denervated glands also increased the responses to 6-OH-DA, while atropine had a feeble blocking action. For all these responses, the adrenal catecholamines played no role. After two consecutive doses of 6-OH-DA a third dose of the drug still elicited a secretory response that was 50% of that of the first dose. It is concluded that for the responses to 6-OH-DA the leakage of noradrenaline from the degenerating adrengic nerve endings of the submaxillary gland plays a partial role. Noradrenaline released by the drug from other tissues and reaching the gland via the circulation also contributes to the responses observed. A muscarinic component may also participate in the secretory effects of 6-OH-DA.

The sialagogue response of striatal dopamine receptors to L-dopa is not influenced by castration or chronic estrogen treatment.

The secretory response of salivary glands to L-dopa, elicited by stimulation of dopamine receptors in the striatum and the circling behavior induced by apomorphine in animals bearing a unilateral kainic lesion of the entopeduncular nucleus, was studied in intact and ovariectomized female rats. Castration did not modify the sialagogue response to L-dopa, while the turning behavior was significantly increased. Daily administration of 17-beta-estradiol benzoate during 7 days to ovariectomized rats decreased the circling activity to the level of intact female rats, while the salivary secretion to L-dopa was unaffected. The above findings suggest that the sialagogue response induced by L-dopa may be due to the interaction of this agonist with D1 striatal receptors, whose activity is not influenced by estrogens. However, we cannot rule out any possible alteration in the metabolism and/or presynaptic conversion of L-dopa to dopamine by estrogen treatment. The changes in turning behavior may be attributed to an antidopaminergic effect of estrogens and/or, like L-dopa, to modifications in the metabolism of apomorphine induced by the hormone.

Effects of 6-hydroxydopamine Treatment at birth on the submaxillary gland of the rat.

Six and 18 months after neonatal administration of 6-hydroxy-dopamine or surgical sympathetic denervation the submaxillary gland of the rat showed a marked depletion of noradrenaline stores. Six months afer removal of the superior cervical ganglion the gland's endogenous noradrenaline was lowered to 0.032 +/- 0.004 mug/g while after neonatal 6-hydroxydopamine the values were 0.228 +/- 0.023 mug/g (controls 2.145 +/- 0.382 mug/g). Eighteen months after either type of sympathetic denervation the neurotransmitter was still depleted. In rats treated with 6-hydroxydopamine the sailagogue effect of injected noradrenaline was potentiated 2.7-fold while the potentiation of the effect of noradrenaline was 3.6 times after surgical denervation. The magnitude of the supersensitivity developed to isoprenaline did not differ between both types of denervation. No supersensitivity to the cholinomimetic agent, methacholine, was observed. Cocaine administration or removal of the superior cervical ganglion slightly increased the supersensivity to noradrenaline in rats treated with 6-hydroxydopamine. Eighteen months after surgical or chemical denervation, the activity of choline-acetyl-transferase in the submaxillary gland was increased by about 50%. Of the respiratory enzymes studied, sussinic dehydrogenase, fumarase and cytochrome oxidase, the activity of only the latter was markedly reduced by a chronic sympathetic denervation. From the results obtained it is concluded that neonatal treatment with 6-hydroxy-dopamine causes a permanent and almost complete sympathectomy of the submaxillary gland of the rat.

Modulation by somatostatin of rat parotid salivary secretion stimulated by cholinergic, adrenergic and peptidergic agents.

Although it is well known that somatostatin (SRIF) modulates several digestive functions, there are only a few reports about its effect on the salivary glands. Here, the action of SRIF parotid secretion was studied, in vivo and in vitro, in male Wistar rats. In vivo SRIF infusion (35 microg/kg per hr) inhibited the parotid flow rate stimulated by methacholine, substance P and noradrenaline. The isoprenaline-stimulated flow rate was also decreased by SRIF, but only at highest dose of the secretory agent. Total protein and amylase secretion were studied. SRIF inhibited the total protein secretion stimulated by the above-mentioned agents, except that by isoprenaline. SRIF did not inhibit in vivo amylase secretion. In order to avoid flow-rate interference with total protein and amylase measurements, in vitro experiments were performed. SRIF (25 nM) strongly inhibited the total protein release stimulated by methacholine (5.1 microM), noradrenaline (19 microM), and substance P (10 microM). The inhibitory effect was not raised by the absence of calcium in the incubation medium. However, in vitro amylase release was not affected by SRIF. It was concluded that SRIF modulates rat parotid secretion stimulated by cholinergic, adrenergic and peptidergic agents, acting on any step in the calcium pathway.

Modulation by somatostatin of rat submandibular salivary secretion.

Although somatostatin (somatotrophin release inhibitory factor; SRIF) is a well-known inhibitory peptide, there are only a few reports of it acting as a positive modulator. In this work, the action of somatostatin upon rat submandibular protein secretion was studied. In vivo somatostatin infusion (35 microg/(kg h)) raised protein secretion stimulated by adrenergic and peptidergic agents. To rule out possible systemic effects of somatostatin, in vitro experiments were performed. Somatostatin (90 nmol/l) augmented protein release stimulated by noradrenaline (19 micromol/l) and substance P (10 micromol/l), but it did not affect isoprenaline (400 micromol/l)-induced protein release. Phenoxybenzamine (20 micromol/l) reduced the effect of somatostatin on noradrenaline-stimulated protein release. Propranolol (20 micromol/l) increased the noradrenaline-stimulated protein release and this effect was synergistic with the action of somatostatin. The absence of extracellular calcium did not significantly reduce somatostatin enhancement of agonist-induced secretion. Fluorescence measurements of the Ca(2+)-sensitive dye fluo3 showed that cytosolic calcium in acinar cells remained elevated during stimuli when somatostatin was present in the medium. It was concluded that somatostatin modulates rat submandibular protein secretion by prolonging the time that the cytosolic calcium signal remains high after stimulus.

Effects of an experimental diet on parotid saliva and dental plaque pH in institutionalized children.

Sixty-six children aged 6-12, permanent residents of a children's home, were placed on a diet during a 45-day experimental period to measure salivary flow-rate, pH of saliva and dental plaque, total concentrations of salivary proteins, inorganic phosphate, bicarbonate, calcium and amylase. The total caloric content, as well as the proportional nutrient and calorie distribution of the foods, were determined and compared with those of the previous habitual diet. After the experimental period, stimulated parotid salivary flow, increased by 40 per cent over the pre-experimental values. Total proteins of saliva and pH of both saliva and dental plaque increased significantly, whereas inorganic phosphate concentration decreased. Concentrations of bicarbonate, calcium and amylase did not differ from those found pre-experimentally. The findings appear to derive from lesser retention and increased hardness of the foods in the experimental diet.

Changes in human parotid salivary protein and sialic acid levels during pregnancy.

Saliva was collected with a Carlson-Crittenden device, under citric acid stimulation, in 107 pregnant women, 9 puerperal and 7 non-pregnant controls. No significant changes were found in salivary flow rate, pH and amylase levels. The total protein levels were decreased during pregnancy and the puerperium. The sialic acid levels decreased gradually but markedly during pregnancy, returning to normal levels in the puerperium. These changes in parotid saliva may be related to the hormonal changes of pregnancy.

Effects of isoproterenol on I131 uptake by the submaxillary glands in mice.

DL-isoproterenol hydrochloride (1 mg/kg body weight/day) was subcutaneously administered to male A2G mice during 15 or 45 days. The sympathetic superior cervical ganglion of each mouse was resected on the right side, two days before beginning the injections. At the end of the injection period, the I131 submaxillary/plasma ratios and I131 thyroid uptake (%) were measured 3 hours after a tracer dose. The administration of isoproterenol induced marked hypertrophy in both normal and denervated submaxillary glands. At 15 days the I131 submaxillary/plasma ratios of the isoproterenol treated mice were slightly decreased on the normal side and were not modified on the denervated side. At 45 days the I131 submaxillary/plasma ratios were markedly decreased on both sides. The thyroid weight and I131 uptake were not modified by the isoproterenol treatment.

Hyposialorrhea as an early manifestation of Parkinson disease.

We sought to determine whether hyposialorrhea is an early manifestation of Parkinson disease (PD). We measured basal and citric acid stimulated secretion of whole saliva in 20 patients with early stage (Hoehn-Yahr I-II) PD who had motor symptoms for less than 1 year and were on no medication and 11 age matched controls. Compared to controls, PD patients had significant reduction of both basal (0.0964+/-0.08 vs 0.293+/-0.112 ml/min, p<0.001) and reflex (0.263+/-0.213 vs 0.537+/-0.313 ml/min, p<0.001) salivary secretion. Our findings confirm that hyposialorrhea is an early autonomic manifestation of PD.