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PubMed1990

In vivo pharmacology of [beta Ala8]neurokinin A-(4-10), a selective NK-2 tachykinin receptor agonist.

We studied the effect of [beta Ala8]neurokinin A-(4-10), a newly developed selective NK-2 tachykinin receptor agonist, on various parameters in anaesthetized rats (blood pressure, urinary bladder motility, plasma extravasation) and guinea-pigs (salivation, increase of pulmonary insufflation pressure) as compared to the response produced by tachykinins. [beta Ala8]Neurokinin A-(4-10) was as active as, or more active than, neurokinin A (NKA) or NKA-(4-10) in producing rat bladder contraction or bronchospasm in guinea-pigs, two effects known to involve activation of NK-2 receptors. On the other hand, the synthetic peptide was weakly active, if active at all, in producing hypotension or plasma extravasation in the rat bladder as well as salivation in guinea-pigs, effects known to involve activation of NK-1 receptors. These findings provide evidence that [beta Ala8]NKA-(4-10) acts as a selective NK-2 agonist in vivo and that it can be used to explore the distribution and function of NK-2 receptors.

Anesthesia↗
PubMed1993

Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats.

The effects of physostigmine, tacrine and NIK-247 on scopolamine-induced impairment of a passive avoidance response were examined in rats. In addition, we investigated possible peripheral side-effects: miosis and salivation, and central side-effects: hypothermia and tremor which are mediated by cholinergic activation. Intraperitoneal injection of physostigmine reversed scopolamine-induced amnesia at a dose of 0.03 mg/kg. Antiamnesic effects of oral administration of tacrine and NIK-247 were observed at doses of 0.3 and 0.1-0.3 mg/kg, respectively. Intraperitoneal injection of physostigmine induced miosis, salivation, hypothermia and tremor at doses > or = 0.1, 0.3, 0.3 and 1 mg/kg, respectively. Oral administration of tacrine (at doses > or = 0.3 mg/kg) and NIK-247 (at doses > or = 3 mg/kg) produced miosis. Tacrine (at doses > or = 1 mg/kg) and NIK-247 (at doses > or = 3 mg/kg) produced hypersalivation. Hypothermia and tremor were observed after administration of tacrine (at doses > or = 10 mg/kg) and NIK-247 (30 mg/kg). The antiamnesic dose of physostigmine was 1/30-1/3 of doses with central or peripheral side-effects. The dose ratio of tacrine was 1/30-1; that of NIK-247 was 1/300-1/10. These results indicate that NIK-247 has higher safety and greater selectivity for cognitive functions than physostigmine or tacrine.

Administration, Oral↗
PubMed1987

Salivary response to esophageal acid in normal subjects and patients with reflux esophagitis.

We studied the effect of esophageal acid perfusion on salivation in patients with reflux esophagitis and in normal subjects. Serial 10-min saliva collections were obtained by expectoration during perfusion of the esophagus with water, and then 0.1 N HCl (pH 1.2) for 50 min or 0.01 N HCl (pH 2.1) for 120 min. Within 1-5 min of beginning 0.1 N HCl perfusion, all 8 patients with esophagitis developed heartburn accompanied by an increase in saliva flow. By the time the severity of heartburn required discontinuation of HCl perfusion (10-40 min), saliva flow had increased nearly fourfold. With 0.1 N HCl perfusion, 8 of 10 volunteers developed mild heartburn after 22 +/- 3 min (mean +/- SE), whereas 0.01 N HCl induced heartburn in 6 of 10 volunteers after 57 +/- 12 min of perfusion. Saliva flow increased concurrently with the onset of heartburn and doubled in those volunteers who developed heartburn. Saliva flow did not change in those volunteers who were without heartburn. We conclude that esophageal acid perfusion unaccompanied by heartburn does not affect salivation. However, saliva flow increases concurrently with the onset of heartburn, a phenomenon called "water brash" when clinically evident. The increased saliva flow that accompanies heartburn may act as an endogenous antacid that serves as a protective response to symptomatic gastroesophageal reflux.

Acids↗
PubMed1987

Oral scopolamine hydrobromide solution as an antisialagogic agent in dentistry.

Antisialagogue, cardiac, and subjective effects of oral scopolamine hydrobromide solution (ScHBr), 0.02 mg/kg total body weight, were studied in a double-blind, randomized, placebo-controlled manner with ten healthy volunteers. ScHBr was rinsed in the mouth for 5 minutes before swallowing. ScHBr reduced nonstimulated and paraffin-stimulated salivation at 40 minutes by 52% and 62%, and at 60 minutes by 81% to 80%, respectively. The heart rate decreased significantly (p less than 0.01) when compared with placebo. With the same drug dosing method, the effects of ScHBr also were tested in clinical dental examination procedures in two dental student groups. In the ScHBr group, salivation decreased by 70%, and in the placebo group, it increased by 22% as a result of mechanical stimulus. Subjective sedation and relaxation were experienced by most of the volunteers.

Administration, Oral↗
PubMed1992

Habituation and dishabituation of human salivary response.

Habituation may be relevant for understanding how sensory stimuli influence factors related to ingestive behavior. In the first of three experiments in humans we showed that salivation and hedonic ratings to lemon or lime juice habituated within 10 presentations, and dishabituation of the salivation and hedonic ratings to the original juice were observed after a new juice was presented. Experiment 2 replicated the habituation and decrease in hedonics to lemon juice, and showed both dishabituation and a relative increase in hedonics when chocolate taste, rather than another juice, served as the dishabituating stimulus. In a third experiment we showed a video game, a nontaste stimulus, could serve as a distractor to prevent the development of habituation, as well as a dishabituator after habituation had occurred.

Adolescent↗
PubMed1995

Physiological and subjective responses to food cues as a function of smoking abstinence and dietary restraint.

Dietary restraint is a characteristic associated with greater increase in food intake after smoking cessation, and salivation is a marker of physiological responsiveness to food that may be influenced by cessation. The present study examined the effect of brief smoking abstinence (16 h) vs. no abstinence on salivary and subjective responses to food taste cues in women smokers high vs. low in dietary restraint (n = 10 each). On each of two days (smoking abstinence vs. nonabstinence), salivary volume was assessed during each of 10 trials involving presentation of a small sample of strawberry yogurt. Decline in salivation over trials is indicative of habituation, or reduction in physiological responsiveness to taste cues, and may be a marker of satiety. Subjects also completed self-report measures of hunger, taste liking, desire for cigarette, and emotional arousal during each trial. A 10-min period of ad lib consumption of yogurt ended each session. Results showed significantly elevated salivary response to the first trial of taste exposure in high vs. low restraint women, especially on the smoking day. Moreover, salivary habituation was significantly disrupted by smoking abstinence, especially over the first 5 trials, in high restraint but not low restraint women. High restraint women also reported increasing desire for cigarette and emotional arousal across food taste trials on both days, while low restraint women reported no change in each over trials. There were no differences in ad lib yogurt consumption. These results indicate that brief smoking abstinence attenuates salivary habituation to taste in high restraint women, suggesting a marker for processes responsible for increased food intake after quitting smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Interrelationships between heat acclimation and salivary cooling mechanism in conscious rats.

1. Adaptation of salivary cooling mechanism during acclimation to heat (34 degrees C) and its role in thermoregulation of the rats was studied on conscious rats with either one submaxillary gland chronically cannulated or both submaxillaries ligated. 2. During heat stress (40 degrees C) acclimated rats showed a decrease both in rectal temperature threshold for salivation (Tre-TS), in salivary flow rate and in Tre (hyperthermic plateau). Animals survived for extended periods and rats with ligated glands survived 40% less than non-ligated rats. 3. For both cannulated and ligated rats short term acclimation (5 days) was the most effective. 4. It is suggested that earlier activation of salivation mechanism is associated with the decreased hyperthermic plateau and that the decreased salivary flow rate allows better control of water balance of the animals. Consequently, survival period during heat stress is extended.

Acclimatization↗
PubMedDate not supplied

The effects of calories and taste on habituation of the human salivary response.

The present study examined the effects of calories on salivary habituation. The rate of habituation to lemon taste was studied over 10 trials in 24 normal weight, nondieting, 18-35-year-old females. Between each of the trials, half the subjects ate low calorie, lemon gelatin, total Kcal = 32, and the others ate high calorie, lemon gelatin, total Kcal = 320. A dishabituating, novel chocolate taste was presented on trial 11 and recovery of salivation was assessed by presenting lemon flavor on trial 12. Subjective ratings were taken before and after salivary habituation for hunger levels and hedonics for lemon taste. Results show that high- and low-calorie groups both habituated to the repeated presentation of lemon taste, but with no significant differences as a function of calories in salivation volume, rate of habituation, hunger level decreases, and hedonic decreases. Subjects in both groups perceived equal caloric intake. These results suggest that salivary habituation may be affected more by the sensory characteristics of the food than by differences in caloric intake. The generalization of these data to the development of satiety are discussed.

Adolescent↗
PubMedDate not supplied

Effects of aging on morphine withdrawal in the rat.

Little is known about the effects of aging on the process of opiate dependence and withdrawal in the rat. The present study was undertaken to quantitate naloxone-precipitated opiate withdrawal in young (3-4 months old) and aged (24 month old) Long-Evan female rats. Following addiction to morphine, young and aged rats were evaluated for tail skin temperature (TST), rectal temperature (Tr), behavior, rhinorrhea, lacrimation, salivation, and diarrhea in response to naloxone administration. Young rats showed the expected TST increase and Tr decline in response to withdrawal. By contrast, aged rats showed two distinct TST response subgroups. The majority of aged rats showed an exaggerated TST response to naloxone, while some aged rats failed to exhibit any TST response to withdrawal. This latter subgroup showed significantly lower basal Tr than either the young rats or the aged-responders. The behavioral activating effects of opiate withdrawal were blunted in aged rats, and these old animals showed a marked decline in rhinorrhea, lacrimation, and salivation during withdrawal. The diarrheal response during withdrawal was not substantially different between the two groups. Collectively, these data indicate that aged female rats exhibit markedly different responses to opiate withdrawal than do their young counterparts.

Aging↗
PubMed2005

Opposite effects of antidepressants on unstimulated and stimulated salivary flow.

In this study, effects on both stimulated and non-stimulated salivary flow as well as salivary components of different antidepressant drugs were compared. Rats received imipramine (IMI; 10mg/ml), fluoxetine (FLU; 20 mg/ml) or moclobemide (MOC; 30 mg/ml) by gavage. The drugs were administered 24, 5 and 1 h before saliva collection (sub-acute treatment) or as a once a day treatment for 14 days (chronic treatment). Animals were sedated with thiopental and saliva was collected using pre-weighed cotton balls inserted in the mouth for 1 min before and after pilocarpine stimulus. Pilocarpine-stimulated saliva was also collected for biochemical assays of total proteins, amylase, phosphate and calcium, performed through automated colorimetric methods. Non-stimulated salivary flow was decreased by sub-acute IMI 10 mg/kg treatment. Pilocarpine-stimulated salivary flow was significantly increased by acute treatments with IMI, FLU and MOC in comparison to the control group. The same opposite pattern of effects on non-stimulated and pilocarpine-stimulated salivation was seen after chronic treatment with the antidepressants. Increased levels of calcium following sub-acute treatment with IMI and after prolonged treatment with FLU and MOC were detected. In the assayed samples, phosphate was found to be increased following chronic treatment with FLU or MOC. These results may explain the discrepant effects of the antidepressants on salivation described in pre-clinical and clinical studies.

Amylases↗
PubMed2006

Protein free diet feeding: effects on sympathetic activity and salivary evoked secretion in the submandibular gland of the rat.

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.

Adrenergic alpha-Agonists↗
PubMed2005

Effects of Byakko-ka-ninjin-to on salivary secretion and bladder function in rats.

Byakko-ka-ninjin-to (BN) is a Kampo medicine (traditional Japanese medicine) that is frequently used to treat xerostomia, which is also a side effect of anticholinergic agents such as oxybutynin and propiverine widely used for the treatment of patients with urinary incontinence or frequency. We investigated the effects of BN on salivation and bladder function in rats, in the presence and absence of oxybutynin. Treatment with BN alone resulted in a slight increase in salivary secretions. In contrast, pilocarpine, a known muscarinic agonist, produced a significant increase in salivary secretions that could be blocked by pretreatment with oxybutynin. A single oral dose of BN at 200mg/kg body weight just before oxybutynin treatment resulted in less inhibition by oxybutynin of pilocarpine-induced salivation. However, BN had no effect on the decreased amplitude of bladder contractions that result from oxybutynin administration. These results suggest that BN might be useful for the xerostomia induced by anticholinergic agents, without influencing their beneficial effect on micturition.

Animals↗
PubMed2004

Continuous recording of excretory water loss from Musca domestica using a flow-through humidity meter: hormonal control of diuresis.

Water loss from adult male houseflies was continuously recorded using a flow-through humidity meter, which enabled losses to be apportioned between the sum of cuticular and respiratory transpiration, salivation and excretion. Transpiration accounted for >95% of water lost from sham-injected flies, compared with excretion (3.0%) and salivation (2.4%). In contrast, excretion accounted for 40% of water lost from flies injected with > or =3 microl of saline, whereas salivary losses were unchanged. Saline injections (1-5 microl) expanded the abdomen in the dorsal-ventral plane, and this expansion was positively correlated with the magnitude of the ensuing diuresis, suggesting the signal for diuretic hormone release originates from stretch receptors in abdominal tergal-sternal muscles. The effects of decapitation, severing the ventral nerve cord within the neck or ligaturing the neck, showed the head was needed to initiate and maintain diuresis, but was neither the source of diuretic hormone nor did it control the discharge of urine from the anus. These findings indicate the head is part of the neural-endocrine pathway between abdominal stretch receptors and sites for diuretic hormone release from the thoracic-abdominal ganglion mass. Evidence is presented for Musdo-K having a hormonal role in the control of diuresis, although other neuropeptides may also be implicated.

Animals↗
PubMed2005

Effects of allocation of attention on habituation to olfactory and visual food stimuli in children.

Responding to food cues may be disrupted by allocating attention to other tasks. We report two experiments examining the effects of allocation of attention on salivary habituation to olfactory plus visual food cues in 8-12-year-old children. In Experiment 1, 42 children were presented with a series of 8 hamburger food stimulus presentations. During each intertrial interval, participants completed a controlled (hard), or automatic (easy) visual memory task, or no task (control). In Experiment 2, 22 children were presented with 10 presentations of a pizza food stimulus and either listened to an audiobook or no audiobook control. Results of Experiment 1 showed group differences in rate of change in salivation (p=0.014). Children in the controlled task did not habituate to repeated food cues, while children in the automatic (p<0.005) or no task (p<0.001) groups decreased responding over time. In Experiment 2, groups differed in the rate of change in salivation (p=0.004). Children in the no audiobook group habituated (p<0.001), while children in the audiobook group did not habituate. Changes in the rate of habituation when attending to non-food stimuli while eating may be a mechanism for increasing energy intake.

Attention↗
PubMed1996

Effects of short-term (2 weeks) streptozotocin-induced diabetes on acetylcholine and noradrenaline in the salivary glands and secretory responses to cholinergic and adrenergic sialogogues in mice.

Acetylcholine and noradrenaline concentrations in the submandibular, parotid and sublingual glands, and pilocarpine-, isoproterenol- and phenylephrine-induced salivation, were estimated in streptozotocin (STZ)-induced diabetic mice. Diabetic mice showed significant increases in acetylcholine and noradrenaline (expressed as nmol/gland) in sublingual and submandibular glands, respectively. The total volume of crude whole saliva in diabetic mice in response to pilocarpine and isoproterenol but not to phenylephrine was significantly reduced. These results suggest that alterations in the neurotransmitter levels and secretory function in the salivary glands occur rapidly after the induction of STZ diabetes, and that the secretory function appears to be more susceptible to effects of diabetes in the early stages than the autonomic nervous system. Since the alterations in neurotransmitter concentrations in diabetic salivary glands were slight and partial, it seems that they are unrelated to the markedly reduced salivation in response to pilocarpine and isoproterenol observed in these short-term diabetic mice.

Acetylcholine↗
PubMed1998

Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamic of tolterodine.

OBJECTIVE: To determine whether cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of tolterodine by investigating potential differences in pharmacokinetics and pharmacodynamic (heart rate, accommodation, and salivation) of tolterodine and its 5-hydroxymethyl metabolite between poor metabolizers and extensive metabolizers of debrisoquin (INN, debrisoquine). METHODS: Sixteen male subjects (eight extensive metabolizers and eight poor metabolizers) received 4 mg tolterodine by mouth twice a day for 8 days followed by a single intravenous infusion of 1.8 mg tolterodine for 30 minutes after a washout period. Doses were given as the tartrate salt. The pharmacokinetics of tolterodine and 5-hydroxymethyl metabolite were determined, and the pharmacodynamic were measured. RESULTS: The mean systemic clearance of tolterodine was significantly lower (p < 0.001) among poor metabolizers (9.0 +/- 2.1 l/hr) compared with extensive metabolizers (44 +/- 13 L/hr), resulting in a fourfold longer elimination half-life (p < 0.001). The terminal half-life of the 5-hydroxymethyl metabolite (2.9 +/- 0.4 hours) was slightly longer than that of the parent compound (2.3 +/- 0.6 hours) among extensive metabolizers, but the 5-hydroxymethyl metabolite was undetectable in the serum of poor metabolizers. Only minor differences in pharmacodynamic effects after tolterodine dosage were observed between the groups. Tolterodine caused a similar decrease in salivation in both panels. The decrease occurred when the concentration of unbound tolterodine and 5-hydroxymethyl metabolite among extensive metabolizers was comparable with that of tolterodine among poor metabolizers. CONCLUSIONS: Tolterodine is extensively metabolized by CYP2D6 with high specificity. Despite the effect on pharmacokinetics, the CYP2D6 polymorphism does not appear to be of great importance in the antimuscarinic effect, probably because of the additive action of parent drug and active metabolite.

Administration, Oral↗
PubMed2001

Investigations into the physiological role of muscarinic M2 and M4 muscarinic and M4 receptor subtypes using receptor knockout mice.

Determination of muscarinic agonist-induced parasympathomimetic effects in wild type and M2 and M4 muscarinic receptor knockout mice revealed that M2 receptors mediated tremor and hypothermia, but not salivation. The M4 receptors seem to play a modest role in salivation, but did not alter hypothermia and tremor. In the M2 knockout mice, agonist-induced bradycardia in isolated spontaneously beating atria was completely absent compared to their wild type litter mates, whereas agonist-induced bradycardia was similar in the M4 knockout and wild type mice. The potency of carbachol to stimulate contraction of isolated stomach fundus, urinary bladder and trachea was reduced by a factor of about 2 in the M2 knockout mice, but was unaltered in the M4 knockout mice. The binding of the muscarinic agonist, [3H]-oxotremorine-M, was reduced in cortical tissue from the M2 knockout mice and to a lesser extent from the M4 knockout mice, and was reduced over 90% in the brain stem of M2 knockout mice. The data demonstrate the usefulness of knockout mice in determining the physiological function of peripheral and central muscarinic receptors.

Animals↗
PubMed1987

Salivary response to olfactory food stimuli as a function of dietary restraint and body weight.

The effects of food and non-food odors on salivation rate and the relation between this response, body weight for height and dietary restraint score were investigated in college students. Potential confounding variables, such as dieters' anxiety due to expectations of food consumption, intrusive methods of salivation collection, and the degree of dieting strictness, were controlled. Results indicated that dietary restraint, but not body weight per se, predicted hyper-responsiveness to food cues, supporting the view that self-imposed dietary restriction heightens external salivary responsiveness to food-related stimuli.

Adult↗