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.

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.

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.

Thyrotropin receptor antibodies in parotid saliva.

Parotid saliva was collected with a Carlson-Crittenden device, under citric acid stimulation, in 18 patients with autoimmune thyroid disease. Thyrotropin Receptor Antibodies (TRAb) were measured with a radioreceptor assay in parotid saliva and in serum in the same patients, and a statistical analysis of the data was performed. TRAb levels in parotid saliva were higher than in serum in the 3 pathologies studied (Graves' disease, Hashitoxicosis and Hashimoto's thyroiditis). There was good correlation between salivary and serum levels.

Effect of testosterone on proteoglycans in the submandibular glands of the rat.

The proteoglycans in the submandibular salivary glands of castrated male Wistar rats were studied before and after the daily administration of testosterone propionate (TP) for one month. Castration decreased the weight of the glands and their uronic acid content. The administration of TP reversed these effects. Chromatographic separation of the uronic acid fractions was performed on cellulose microcolumns. The principal fractions were hyaluronic acid, heparan sulfate and dermatan sulfate. There were also changes in the physical properties of the proteoglycans. Castration decreased the range of distribution of molecular weight and the density, while the lateral chains of smaller length disappeared. TP administration to castrated rats reversed these effects.

Effects of castration and androgens upon prostatic proteoglycans in rats.

In studies performed on male Wistar rats, castration induced atrophy of the prostate with a marked increase in the uronic acid content. The administration of testosterone propionate to castrated rats produced opposite effects. Fractionation of the glycosaminoglycans on cellulose microcolumns showed that the changes in uronic acid content in the dorsolateral lobes were due to variations in hyaluronic acid, chondroitin-4-sulfate, and dermatan sulfate, but in the ventral lobes, there were changes in all the chromatographic fractions. There were also changes in the physical properties of proteoglycans. In the ventral lobes, castration induced a wider distribution of molecular weight, increased density, and predominance of lateral chains of greater size. In the dorsolateral lobes, there was a decrease in molecular weight and density of proteoglycans and in the length of lateral chains. Opposite results were obtained when testosterone propionate was given to castrated rats. It is postulated that the effects of androgens upon prostatic growth would depend on an interrelationship between epithelium and stroma mediated by the proteoglycans.

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.

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.

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.

Changes in pancreatic exocrine secretion after repeated haloperidol administration.

The effect of repeated administration of haloperidol on the pancreatic secretion was studied in urethane-anesthetized Swiss mice. Haloperidol (2 mg/kg) injected daily i.p. for 7 days, increase the volume and protein content of the basal pancreatic juice significantly. This secretory activity was partially blocked by i.p. injection of atropine (5 mg/kg), both in control and treated animals. The volume of the secretory response to bethanechol, a cholinergic agonist, was decreased by haloperidol without any change in amylase release. From these findings it is concluded that repeated haloperidol treatment produces an increase of basal pancreatic secretion, which is probably the result of changes in the sensitivity of dopamine receptors of the gland.

Increase of muscarinic cholinergic receptors in the rat submandibular glands after parasympathectomy and repeated administration of haloperidol.

1. The mechanisms of the supersensitivity to cholinergic drugs after chronic haloperidol was studied in normal and parasympathectomized submandibular glands of the rats. 2. Both parasympathectomy and haloperidol treatment for 7 days (2 mg/kg/day, i.p.) increased the sialogogue response of the glands to methacholine, a cholinomimetic drug. 3. Both denervation and haloperidol administration induce up-regulation of the muscarinic receptors as expressed per gram of the tissue. 4. Haloperidol causes no further increase in sensitivity than denervation alone. 5. These data demonstrate that secretory supersensitivity to cholinergic drugs in the rat submandibular glands, after chronic haloperidol and parasympathectomy is related to an increase in muscarinic cholinergic receptors.

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.

Synthesis and contents of pancreatic exportable enzymes. Effect of oleic acid intraduodenal administration.

The effect of intraduodenal oleic acid administration on protein synthesis and enzymatic levels in rat pancreas was investigated. Sprague-Dawley rats were sacrificed at 20, 40, 60, and 80 min after intraduodenal oleic acid administration. Ten minutes before sacrifice, the rats were injected with 50 microCi 3H-Phenylalanine intraperitoneally. Amylase (Am), chymotrypsinogen (Chtg), trypsinogen (Tg) and lipase (Li) activities, and 3H-Phenylalanine incorporation to total secretory proteins were determined in pancreas homogenates. Forty minutes after oleic acid administration, the activities of Chtg, Tg and Li were significantly increased (45, 38 and 23%, respectively) above those from control rats. Amylase levels were not modified. Enzyme activities decreased below baseline levels by 60 and 80 min after oleic acid administration. The 3H-phenylalanine incorporation pattern exhibited a peak at 40 min. We conclude that intraduodenal oleic acid administration stimulates intrapancreatic enzyme content in a non-parallel fashion, before enzyme activities decreased below those from control rats. Protein synthesis was similarly affected by intraduodenal oleic acid.

Synthesis and contents of pancreatic exportable enzymes. Effect of oleic acid intraduodenal administration.

The effect of intraduodenal oleic acid administration on protein synthesis and enzymatic levels in rat pancreas was investigated. Sprague-Dawley rats were sacrificed at 20, 40, 60, and 80 min after intraduodenal oleic acid administration. Ten minutes before sacrifice, the rats were injected with 50 microCi 3H-Phenylalanine intraperitoneally. Amylase (Am), chymotrypsinogen (Chtg), trypsinogen (Tg) and lipase (Li) activities, and 3H-Phenylalanine incorporation to total secretory proteins were determined in pancreas homogenates. Forty minutes after oleic acid administration, the activities of Chtg, Tg and Li were significantly increased (45, 38 and 23

, respectively) above those from control rats. Amylase levels were not modified. Enzyme activities decreased below baseline levels by 60 and 80 min after oleic acid administration. The 3H-phenylalanine incorporation pattern exhibited a peak at 40 min. We conclude that intraduodenal oleic acid administration stimulates intrapancreatic enzyme content in a non-parallel fashion, before enzyme activities decreased below those from control rats. Protein synthesis was similarly affected by intraduodenal oleic acid.

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.

Effect of chronic administration of haloperidol on secretory response mediated by cholinergic receptors in rat submandibular glands.

Administration of haloperidol influences peripheral non-dopaminergic receptors. The sialagogue response of the submandibular glands of the rats to methacholine was enhanced by chronic administration of haloperidol. The binding of [3H]QNB to muscarinic receptors in the submandibular glands was not changed by chronic haloperidol. The supersensitivity of postsynaptic cholinergic receptors to drugs in haloperidol treated rats is not related to changes in the number or affinity of such receptors. This paper confirmed the sialagogue supersensitivity to adrenergic drugs related to an increase in alpha 1-adrenoceptors in the submandibular glands of haloperidol injected rats.

Secreción de amilasa y quimotripsinógeno en la rata diabética por estreptozotocina / Secretion of amylase and chymotrypsinogen in streptozotocin induced diabetic rats

Se ha estudiado el contenido de amilasa y quimotripsinógeno en la secreción pancreática basal y post-estimulación de la rata anestesiada, y en su respectivo homogenado pancreático. Estos valores se han comparado con los provenientes de un grupo de ratas con diabetes por estreptozotocina. La secreción basal de la rata anestesiada tiene una relación amilasa/quimotripsinógeno de 70,3 ñ 1,1, después de la estimulación con ceruleína (600ng/kg) este valor cae a 17,9 ñ 1,9, siendo de 20,3 ñ 1,2 las cifras halladas en el homogenado pancreático. Se confirma de esta manera que la secreción pancreática basal en la rata anestesiada proviene de un compartimiento minoritario, e inversamente la obtenida post-estimulación provendría de un reservorio mayoritario (proporciones enzimáticas similares a las del páncreas total). En los animales diabéticos se ha observado una relación amilasa/quimotripsinógeno de 40,6 ñ 0,6 durante la secreción basal, después de la estimulación con ceruleína esta cifra en el jugo pancreático desciende a 8,7 ñ 0,9, siendo el valor en sus respectivos homogenados pancreáticos de 9,7 ñ 0,9. La diabetes ha provocado una reducción proporcionalmente mayor para la amilasa que para el quimotripsinógeno, en la secreción basal, en la secreción post-estimulación y en el homogenado pancreático. En conclusión, la diabetes modifica el contenido de las enzimas estudiadas con similar intensidad en ambos compartimientos; la insulina no sería probablemente responsable directa de las diferentes proporciones enzimáticas presente en ambos compartimientos secretorios (AU)

Secreción de amilasa y quimotripsinógeno en la rata diabética por estreptozotocina / Secretion of amylase and chymotrypsinogen in streptozotocin induced diabetic rats

Se ha estudiado el contenido de amilasa y quimotripsinógeno en la secreción pancreática basal y post-estimulación de la rata anestesiada, y en su respectivo homogenado pancreático. Estos valores se han comparado con los provenientes de un grupo de ratas con diabetes por estreptozotocina. La secreción basal de la rata anestesiada tiene una relación amilasa/quimotripsinógeno de 70,3 ñ 1,1, después de la estimulación con ceruleína (600ng/kg) este valor cae a 17,9 ñ 1,9, siendo de 20,3 ñ 1,2 las cifras halladas en el homogenado pancreático. Se confirma de esta manera que la secreción pancreática basal en la rata anestesiada proviene de un compartimiento minoritario, e inversamente la obtenida post-estimulación provendría de un reservorio mayoritario (proporciones enzimáticas similares a las del páncreas total). En los animales diabéticos se ha observado una relación amilasa/quimotripsinógeno de 40,6 ñ 0,6 durante la secreción basal, después de la estimulación con ceruleína esta cifra en el jugo pancreático desciende a 8,7 ñ 0,9, siendo el valor en sus respectivos homogenados pancreáticos de 9,7 ñ 0,9. La diabetes ha provocado una reducción proporcionalmente mayor para la amilasa que para el quimotripsinógeno, en la secreción basal, en la secreción post-estimulación y en el homogenado pancreático. En conclusión, la diabetes modifica el contenido de las enzimas estudiadas con similar intensidad en ambos compartimientos; la insulina no sería probablemente responsable directa de las diferentes proporciones enzimáticas presente en ambos compartimientos secretorios