Influence of ruminal and plasma osmotic pressure on salivary secretion in sheep

The osmotic pressure of the rumen contents and also of the blood was altered by intraruminal administration of water or hypertonic solutions. It was found that alterations in osmotic pressure were accompanied by inverse changes in the flow rate of mixed saliva. Intravenous infusion of hypertonic solutions, causing elevation of the osmotic pressure of the blood without affecting that of the rumen, also caused a reduction of salivary secretion rate. The flow rates of both parotid and residual saliva were affected. When strongly hypertonic solutions of sodium or potassium salts were infused into the rumen, or sodium salts or urea were infused into the blood, the concentration of those substances increased in the saliva. Other treatments had little effect on salivary composition.     

The effects of skin pressure by clothing on circadian rhythms of core temperature and salivary melatonin

The present experiment investigated the effects of skin pressure by foundation garments (girdle and brassiere) on the circadian rhythms of core temperature and salivary melatonin. Ten healthy females (18-23 years) maintained regular sleep-wake cycles for a week prior to participation in the experiment. The experiments were performed from June to August 1999 using a bioclimatic chamber controlled at 26.5 degrees C +/- 0.2 degrees C and 62% +/- 3% RH. Ambient light intensity was controlled at 500 lux from 07:30 to 17:30, 100 lux from 17:30 to 19:30, 20 lux from 19:30 to 23:30; there was total darkness from 23:30 to 07:30. The experiment lasted for 58h over three nights. The participants arose at 07:30 on the first full day and retired at 23:30, adhering to a set schedule for 24h, but without wearing foundation garments. For the final 24h of the second full day, the subjects wore foundation garments. Rectal and leg skin temperatures were measured continuously throughout the experiment. Saliva and urine were collected every 4h for the analysis of melatonin and catecholamines, respectively. Skin pressure applied by the foundation garments was in the range 11-17 gf/cm2 at the regions of the abdomen, hip, chest, and back. The main results were as follows: (1) Rectal temperatures were significantly higher throughout the day and night when wearing foundation garments. (2) The nocturnal level of salivary melatonin measured at 03:30 was 115.2 +/- 40.4 pg/mL (mean +/- SEM, N = 10) without and 51.3 +/- 18.4 pg/mL (mean +/- SEM, N = 10) with foundation garments. (3) Mean urinary noradrenaline excretion was significantly lower throughout the day and night when wearing foundation garments (p < .05), but mean urinary adrenaline excretion was not different. The results suggest that skin pressure by clothing could markedly suppress the nocturnal elevation of salivary melatonin, resulting in an increase of rectal temperature.     

Effects of intraventricular administration of vasoactive intestinal peptide and neurotensin on salivary secretion and blood pressure in the rat

Studies were carried out to investigate central actions of vasoactive intestinal polypeptide (VIP) and neurotensin (NT) on systemic blood pressure (BP), heart rate (HR) and salivary secretion in urethane-anesthetized male rats. Intraventricular (i.c.v.) administration of VIP caused dose-related increases in BP, HR and salivary secretion. Nearly maximum values were obtained at the dose of 2.0 micrograms for BP and 10.0 micrograms for salivary secretion, whereas the increase in HR did not attain the maximum even with the dose of 10.0 micrograms. Administration of hexamethonium (i.v.) completely blocked the increasing response of BP and HR, and the administration of pimozide (i.p.) or phenoxybenzamine (i.v.) reduced them. The increasing response of salivary secretion was almost completely blocked by all of the drugs. The administration of NT (i.c.v.) produced no change in the BP, HR and salivary secretion. The present results indicate that, 1) centrally administered VIP may somehow augment the sympathetic nerve discharge and/or adrenal medulla secretion, and 2) central VIP may play a role in the control of salivary regulation, probably through sympathetic nerves.     

Effects of octopamine on fluid secretion by isolated salivary glands of a feeding ixodid tick

Octopamine elicited a dose-related secretory response by salivary glands isolated from the feeding female tick Amblyomma americanum. Half-maximal stimulation occurred at about 60 μM. Phentolamine (10 μM) failed to inhibit the octopamine-mediated response; however, thioridazine (50 μM) inhibited both octopamine (1,000 μM) and dopamine-stimulated (0.1 μM) secretion. Maximal stimulation by dopamine (1.0 μM) showed no further increase in the rate of secretion after adding octopamine (1,000 or 0.1 μM). Glands responded to octopamine (100 μM) with rates significantly lower than controls following exposure to amphetamine (1,000 μM). Octopamine receptors do not appear to mediate the secretory response, and octopamine may stimulate secretion by releasing catecholamines from presynaptic neurons. These results support the hypothesis that dopamine is the natural transmitter mediating fluid secretion in the feeding tick salivary gland.     

Effects of the high-molecular-weight cryoprotectant dextran on fluid secretion by Calliphora salivary glands

The rate of fluid secretion by isolated salivary glands of Calliphora was inhibited as a linear function of dextran and poly vinyl pyrrolidone concentrations in the range 15–35% w/w. This inhibition was not overcome by supramaximal concentrations of 5-hydroxytryptamine, nor was it caused by a decreased availability of K⁺ from the medium. Although the polymers caused large decreases of freezing point (and vapor pressure) of the incubation medium, the glands did not respond to this by secreting a more K ⁺-rich saliva. When dextran and polyvinyl pyrrolidone were added as powders to salt solutions, the total freezing-point depression of the mixture was equal to the sum of that exerted by the pure salt solution and that expected for the polymer concentration. The activities of K⁺ and Cl^?, as measured by ion-selective electrodes, were not increased in solutions by the addition of dextran. Dextran was demonstrated by electron microscopy to penetrate into the basal clefts and intercellular spaces of the isolated glands. These results demonstrate that addition of dextran (and probably of polyvinyl pyrrolidone) does not decrease the solvent activity of water in physiological salt solutions. The inhibition of fluid secretion by isolated salivary glands of Calliphora seems therefore due only to the altered physical characteristics of the medium.     

Autonomic effects on protein secretion by rat submandibular salivary glands

1. Following treatment with cholinergic and beta-adrenergic drugs, the beta-type protein, associated with cAMP, was secreted regardless of the doses used. 2. Following treatment with alpha 1-adrenergic drugs, both the beta-type and alpha-type proteins were secreted depending on the doses used and the alpha-type protein was completely converted to the beta-type with alpha-blockers. 3. Following treatment with alpha 2-adrenergic drugs, the gamma-type protein, associated with cGMP, was secreted independent of the doses used.     

Effects of diabetes mellitus on salivary secretion and its composition in the human

Calreticulin is a Ca2+ binding/storage chaperone resident protein of the endoplasmic reticulum. This protein plays a key role in the calreticulin/calnexin cycle and the quality control pathways in the endoplasmic reticulum. Calreticulin deficiency is lethal due to impaired cardiac development. However, over-expression of the protein in developing and postnatal heart leads to bradycardia, complete heart block and sudden death. Ultrastructural evidence indicates that the deficiency associated with the absence of calreticulin in the heart may be due to a defect in the development of the contractile apparatus and/or a defect in development of the conductive system as well as a metabolic abnormality. Collectively, we postulate that calreticulin and endoplasmic reticulum plays an important role in cardiac development and postnatal pathologies.     

Effects of skin pressure by clothing on digestion and orocecal transit time of food

In order to reveal the influence of clothing skin pressure on digestion of food through the gastrointestinal tract, we examined the absorption of dietary carbohydrate and orocecal transit time of a test meal by means of a breath hydrogen test on 7 healthy young women. In this experiment, we collected breath samples from the participants wearing loose-fitting experimental garment on the second day of the experiment and from the same participants but wearing an additional tight-fitting girdle on the following day for 16 hours and 9 hours, respectively. Skin pressure applied by a girdle on participant's waist, abdomen and hip region was 15.5 +/- 0.4 mmHg (mean +/- SE), 11.0 +/- 0.2 mmHg, and 13.6 +/- 0.6 mmHg, respectively, and the values were 2-3 times larger than those of the experimental garment. The hydrogen concentration vs. time curve showed that breath hydrogen levels at its peaks (15:00, 15:30, 16:00, 16:30, and 17:00 hr) on the third day of the experiment were significantly higher than those of the corresponding time on the second day (p < 0.05 at 17:00 and 15:00, p < 0.01 at 15:00, 16:00 and 16:30). Consequently, significantly pronounced breath hydrogen excretion was observed under the "pressure" clothing condition (p < 0.01). On the other hand, the transit time of the test meal for the subjects wearing a girdle did not differ significantly from that for the subjects wearing the garment of less pressure (270 +/- 18 minutes and 263 +/- 21 minutes, respectively). These results indicate that the clothing skin pressure has an inhibitory effect on the absorption of dietary carbohydrate in the small intestine, but no effect on the orocecal transit time of a meal.     

Inhibition of salivary secretion by activation of cannabinoid receptors

It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CBs) are located in salivary glands to mediate that effect. In these experiments, we used the submandibular gland (SMG) of male rats, which is one of the major salivary glands. Mammalian tissues contain at least two types of CBs, CB1 and CB2, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to Gi protein and respond by inhibiting the activity of adenylyl cyclase. We demonstrated that both CB1 and CB2 are present in the SMG, each showing specific localizations. The best-known endocannabinoid is anandamide (AEA), which binds with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 and AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are implicated in SMG physiology. In addition, we showed that AEA injected intraglandularly to anesthetized rats inhibited norepinephrine (NE)- and methacholine (MC)-stimulated saliva secretion in vivo and that both AM251 or AM630 prevented the inhibitory action of AEA. Also, the intraglandular injection of AM251 increased saliva secretion induced by lower doses of NE or MC. This increase was synergized after coinjection with AM630. Therefore, we concluded that AEA decreases saliva secretion in the SMG acting through CB1 and CB2 receptors.     

Effect of cerulein on human salivary secretion]

To evaluate the effect of cerulein on salivary secretion in man, 25 healthy volunteers have been studied. In the morning, before breakfast, saline solution (125 ml/h) has been infused at a constant flow, for one hour. Saline solution has been followed, for other 60', by saline solution + Cerulein at doses of 0.05, 0.1, 0.2, 0.3, 0.5 microgram/Kg/h. These different doses have been administered in different days according to a randomized order. A wash out by saline solution, at same velocity as before, has been carried out after Cerulein . Samples of saliva were collected every 15'. On salivary specimens the amylase activity (U/l) has been dosed. Each dose of Cerulein induced a reduction of salivary flow. By blocking the administration of Cerulein the salivary secretion returned to basal value in about one hour. No inhibitory effect has been noted on amylase secretion using different doses of Cerulein .     

Calcium antagonists cause dry mouth by inhibiting resting saliva secretion

Ca2+ antagonists cause dry mouth by inhibiting saliva secretion. The present study was undertaken to elucidate the mechanism by which Ca2+ antagonists cause dry mouth. Since the intracellular Ca2+ concentration ([Ca2+]i) is closely related to saliva secretion, [Ca2+]i was measured with a video-imaging analysis system by using human submandibular gland (HSG) cells as the material. The Ca2+ antagonist, nifedipine, inhibited the elevation in [Ca2+]i induced by 1-10 microM carbachol (CCh), but had no inhibitory effect on that induced by 30 and 100 microM CCh. The other kinds of Ca2+ antagonists, verapamil (10 microM), diltiazem (10 microM), and the inorganic Ca2+ channel blocker, CdCl2 (50 microM), also inhibited the [Ca2+]i elevation induced by 10 microM CCh. The Ca2+ channel activator, Bay K 8644 (5 microM), significantly enhanced the CCh (10 microM)-induced [Ca2+]i elevation. Endothelin-1 and norepinephrine also increased the CCh (10 microM)-induced [Ca2+]i elevation. SKF-96365 reversed the enhancement of the CCh (10 microM)-induced [Ca2+]i elevation caused by AlF4- and phenylephrine. The phospholipase Cbeta (PLCbeta) inhibitor, U-73122 (5 microM), significantly inhibited the [Ca2+]i elevation induced by 100 microM CCh compared with that induced by 10 microM CCh, while the PLCbeta activator, m-3M3FBS (20 microM), significantly increased the [Ca2+]i elevation induced by 100 microM CCh compared with that induced by 10 microM CCh. We therefore conclude that non-selective cation and voltage-dependent Ca2+ channels are involved in resting salivation and that Ca2+ antagonists depress H2O secretion by blocking the Ca2+ channels and thereby cause dry mouth.     

Cell biology of human salivary secretion

We treated surgical specimens of human parotid and submandibular glands in vitro to manipulate the receptor-signaling cascade pharmacologically and analyzed cellular responses by light microscopy on epoxy embedded sections. Treatment of specimens with the b-agonist, isoproterenol, and with the second messenger analog, dibutyryl cyclic AMP, stimulated serous acinar cells to engage in exocytosis and degranulation. The muscarinic agonist, carbachol, and the calcium ionophore, A23187, on the other hand, elicited formation of "vacuoles" in the cytoplasm of serous acinar cells. Taking previous in vivo human and animal studies into account, these changes are suggested as the morphological expression of enzyme release and fluid secretion, respectively. Specimens obtained from patients over 70 years old exhibited poor response even though their morphological appearance remained intact. Aged salivary glands are thus suggested to experience a decline in their secretory activity at the cellular level, probably by impairment of the signaling processes downstream to the receptor activation and second messenger production.