Pharmacological analysis of salivary and blood flow responses to histamine of the submandibular gland of the dog.

1 The submandibular gland in situ was perfused with blood through the glandular artery at constant pressure in anaesthetized dogs. Drugs were administered intra-arterially. 2 Histamine produced both salivation and an increase in blood flow, each response having an early and a late component. 3 Marked tachyphylaxis to histamine developed in both of the salivary responses but only in the late blood flow response to histamine. 4 The early and late salivary responses were abolished and the late blood flow response was diminished by infusion of tetrodotoxin in doses that abolished the salivary and blood flow responses to electrical stimulation of the chorda-lingual nerve. 5 The whole salivary response to histamine was abolished by infusion of (--)-hyoscyamine in doses that greatly antagonized the salivary and blood flow responses to acetylcholine, whereas the blood flow responses to histamine were scarcely modified. These doses of (--)-hyoscyamine abolished the salivary response to chorda-lingual nerve stimulation but left the blood flow response to it unaffected. 6 The salivary and blood flow responses to histamine were unaffected by infusion of hexamethonium in doses that almost abolished the salivary and blood flow responses to chorda-lingual nerve stimulation. 7 The whole salivary response to histamine was abolished and the late blood response to histamine was partially inhibited by the histamine H1-receptor antagonist, mepyramine, but not by the histamine H2-receptor antagonist, metiamide. 8 The early blood flow response to histamine was antagonized by both mepyramine and metiamide but mepyramine was far more effective than metiamide. 9 These results led to the following conclusions: (1) the whole salivary response and a part of the late blood flow response to histamine are due entirely to excitation of parasympathetic postganglionic neurones; (2) neuronal histamine receptors involved are exclusively of the H1-type; (3) histamine has no direct stimulant action on the glandular cells; (4) the early blood flow response and the remaining part of the late blood flow response to histamine result from the direct action on vascular smooth muscle in the glandular vascular bed; (5) vascular histamine receptors consist of H1- and H2-receptors.     

Effects of adenosine on adrenergically induced renal vasoconstriction in dogs

The role of exogenous and endogenous adenosine in the neural control of renal blood flow was studied in anesthetized dogs. The plasma norepinephrine (NE) concentration was measured by high-performance liquid chromatography and the renal NE secretion rate was calculated. Renal nerve stimulation (1-3 Hz) reduced renal blood flow and increased NE secretion rate. The intrarenal arterial injection of NE (0.3-1.0 micrograms) also reduced renal blood flow. Infusion of adenosine (10-100 micrograms/min) into the renal artery attenuated the increase in NE secretion rate induced by renal nerve stimulation, but the nerve stimulation-induced decrease in renal blood flow was unaffected. On the other hand, adenosine potentiated the NE-induced renal blood flow response. Similar results were obtained with an adenosine potentiator, dipyridamole (1-10 micrograms/min). An adenosine receptor blocker, theophylline (0.3-1.0 mg/min), potentiated the NE secretion rate response induced by nerve stimulation, without any change in the renal blood flow response. The NE-induced renal blood flow response was attenuated by theophylline. These results suggest that adenosine inhibits neural NE release and enhances vasoconstriction in the dog kidney during sympathetic stimulation under in vivo conditions. These post- and presynaptic mechanisms may thus be activated by endogenous adenosine.     

Assessment of the effects of vasoactive intestinal peptide (VIP) on blood flow through and salivation of the dog salivary gland in comparison with those of secretin, glucagon and acetylcholine.

1. The vascular bed of the submandibular gland in situ was perfused with blood through the glandular artery at a constant pressure in anesthetized dogs. All drugs were administered intra-arterially. 2. Vasoactive intestinal peptide (VIP), secretin and acetylcholine produced a dose-dependent increase in blood flow through the artery (vasodilatation) but glucagon was almost ineffective. 3. Dose-blood flow response curves for VIP and secretin were parallel, and VIP was about 100 times as potent as secretin on a molar basis. Dose-blood flow response curves for acetylcholine were flatter than those for VIP and secretin. Acetylcholine was approximately as potent as secretin on a molar basis. 4. No tachyphylaxis developed to the vasodilator action of VIP. 5. The vasodilator responses to VIP and to electrical stimulation of the chordolingual nerve were scarcely modified by (-)-hyoscyamine in doses that fully antagonized the vasodilator response to acetylcholine. 6. VIP, secretin and glucagon were ineffective in eliciting salivary secretion. 7. The possibility that VIP is released from parasympathetic vasodilator nerves and mediates the atropine-resistant vasodilatation in the dog submandibular gland is discussed.     

Histamine and calcium secretion in the submandibular gland of the cat evoked by two types of stimulation

The aim of this work was to compare the pools of histamine and calcium in the submandibular gland of the cat during two kinds of stimulation of the gland. Submandibular glands of the cat were stimulated electrically (chorda tympani nerve) and by close arterial infusion of pilocarpine. Each stimulation was adjusted in such a way as to obtain a near maximal secretory response. Concentrations of histamine and calcium were measured in nonstimulated and stimulated glands, in saliva, secreted during stimulation and in the venous outflow from the gland before and during the stimulation. The experiments showed that: pilocarpine stimulation lowered the histamine concentration in the gland more than electrical stimulation of the chorda tympani nerve. Calcium stores in the gland were depleted to the same extent by each type of stimulation. the concentration of histamine and calcium in the saliva produced by close arterial pilocarpine infusion was significantly higher than in the saliva secreted during nerve stimulation. histamine and calcium concentrations were higher in the venous outflow from stimulated glands than before stimulation. The results indicate a close relationship between histamine and calcium in salivary secretion, although the origins of the two substances are different.     

Secretion of IgA by rat parotid and submandibular cells in response to autonomimetic stimulation in vitro

The major antibody in saliva is IgA, which is actively transported by pIgR expressed by parenchymal cells within the salivary glands. The rate of IgA secretion into saliva is regulated by the autonomic nerves supplying the glands in vivo. This study examined the mechanism of increased IgA secretion into saliva with autonomimetic stimulation. In vitro stimulation of IgA secretion from cells prepared by digestion of rat salivary glands found submandibular cell preparations responded to alpha- and beta-adrenergic stimuli whereas the parotid cells responded only to beta-adrenergic stimulation, although cells from both glands responded similarly to cholinergic stimulation. The additional responsiveness of submandibular cells to alpha-adrenergic stimulation probably reflects the presence of granular duct cells (absent in parotid glands) which are known to secrete protein in response to high frequency sympathetic stimulation. The increased secretion of IgA was not dependant upon increased plasma cell activation since isolated salivary gland plasma cells did not respond to agonists. Further evidence for the regulating role of parenchymal cells in IgA secretion into saliva was revealed by analysis of polymeric immunoglobulin receptor (pIgR) levels expressed on cells. Following in vivo nerve stimulation, there was an increased amount of pIgR expressed on the membrane surface. This was functionally demonstrated in vitro by increased uptake of human IgA by acutely prepared rat salivary cells following stimulation by adrenaline, indicating increased mobilisation of pIgR with stimulation. This study confirms that salivary cells increase the delivery of IgA into saliva by a pIgR-mediated mechanism in response to autonomic stimulation.     

The inhibition of salivary secretion by histamine H2-antagonists--a study on the cat submandibular gland

The aim of the present work was to establish whether the secretory process can be influenced by histamine H2-receptor antagonists, burimamide and metiamide. These drugs were applied intravenously and the secretion was evoked by the electrical stimulation of the chorda tympani nerve or by carbachol (i.v.). In addition to the measurements of the flow of saliva, the blood flow through the gland was measured in some experiments. Both H2-antagonists significantly reduced the rate of salivary secretion induced by the chorda tympani stimulation. The experiments with burimamide did not permit the calculation of dose-response relationship. From the experiments with metiamide the ED50 was 4.6 mumols/kg and Emax was 30% reduction of secretion. The secretory response to carbachol was not diminished by burimamide. In addition to the effect of metiamide on salivation, the reduction of the blood flow through the gland was observed: the effect on the blood flow was significantly smaller, and slower in onset, than the effect on salivation. These results support the hypothesis that H2-receptors are involved in the process of salivary secretion. Histamine effects on glandular elements seem to be more significant than its effect on the blood vessels.     

EFFECTS OF ZAPRINAST ON RENAL NERVE STIMULATION-INDUCED ANTI-NATRIURESIS IN ANAESTHETIZED DOGS

1. We examined whether zaprinast, a putative cGMP-specific phosphodiesterase inhibitor, affects neural control of renal function in pentobarbital-anaesthetized dogs. 2. Renal nerve stimulation (1Hz, 1ms duration) reduced urine flow rate, urinary Na⁺ excretion (UNaV) and fractional excretion of Na⁺ (FENa) with little change in either renal blood flow (RBF) or glomerular filtration rate (GFR). 3. Intrarenal arterial infusion of zaprinast (10 and 100 μg/kg per min) increased basal urine flow rate, UNaV and FENa but not RBF or GFR. Zaprinast infusion (100 μg/kg per min) also increased renal venous plasma cGMP concentration and urinary cGMP excretion. 4. Renal nerve stimulation-induced reductions in UNaV and FENa were attenuated during zaprinast infusion, whereas the reduction in urine flow rate was resistant to zaprinast. 5. Renal nerve stimulation increased the renal venous plasma noradrenaline concentration and renal noradrenaline efflux, which remained unaffected during infusion of zaprinast (100 μg/kg per min). 6. The results of the present study suggest that zaprinast induces natriuresis and counteracts adrenergically induced anti-natriuresis by acting on renal tubular sites in the dog kidney in vivo.     

Mechanisms of sympathetic enhancement and inhibition of parasympathetically induced salivary secretion in anaesthetized dogs.

1. The effects of superimposed and continuous sympathetic nerve stimulation on submandibular parasympathetic salivation were investigated in anaesthetized dogs. 2. Superimposed sympathetic nerve stimulation (1-2 min) initially enhanced and later inhibited salivary secretion induced by parasympathetic nerve stimulation (2-8 Hz) in glands with uncontrolled blood supply or constant-flow vascular perfusion. Propranolol (0.05 mg kg-1, i.a.) did not affect the diphasic sympathetic action whereas phentolamine (0.1 mg kg-1, i.a.) abolished it. Prazosin (0.025 mg kg-1, i.a.) greatly lessened the initial enhancement while yohimbine (0.025 mg kg-1, i.a.) alleviated the late inhibition. 3. Salivary secretion, induced by parasympathetic nerve stimulation (4 Hz) or acetylcholine infusion (10 micrograms kg-1 min-1, i.a.), was abolished by atropine (0.05 mg kg-1, i.a.), increased by phenylephrine infusion (0.25 microgram kg-1 min-1, i.a.) and depressed by clonidine infusion (0.75 microgram kg-1 min-1, i.a.). Hexamethionium (12.5 mg kg-1, i.a.) abolished the nerve-induced secretion but had no effect on the acetylcholine-induced secretion. 4. Continuous background sympathetic nerve stimulation decreased parasympathetic nerve-induced salivary secretion in glands with uncontrolled blood supply or constant-flow vascular perfusion. 5. These results show that parasympathetic salivation can be modified by the sympathetic system at the postsynaptic level; enhancement is via alpha 1-adrenoceptors whereas inhibition is via alpha 2-adrenoceptors.     

Effects of adrenergic agents on secretion of salivary kallikrein in the submandibular gland of the dog]

The effects of sympathetic nerve stimulation and administrations of sympathomimetics on the secretion of salivary kallikrein induced by stimulation of Chorda tympani were examined quantitatively and qualitatively in the dog submandibular gland. Both sympathetic stimulation and administrations of sympathomimetics such as norepinephrine, epinephrine, and isoproterenol caused increased secretion of salivary kallikrein. Among these effects, those of the sympathetic stimulation, norepinephrine, and epinephrine were not completely abolished by pretreatment with phenoxybenzamine or propranolol, but the effect of isoproterenol was abolished by pretreatment with propranolol, and was hardly influenced by pretreatment with phenoxybenzamine. From these results, it would appear that secretion of salivary kallikrein may be mediated through adrenergic alpha- and beta-receptors. On the other hand, in contrast with the activities of the salivary kallikrein secreted by Chorda tympani stimulation or administration of isoproterenol which were not inhibited by SBTI, the activities of the salivary kallikrein secreted by sympathetic stimulation as well as administration of norepinephrine or epinephrine were markedly inhibited by SBTI. From these results, it is concluded that secretion of glandular kallikrein is due either to Chorda tympani stimulation or is mediated through adrenergic beta-receptor, while secretion of plasma kallikrein is mediated through adrenergic alpha-receptor.     

Effects of capsaicin pretreatment on neuropeptides and salivary secretion of rat parotid glands.

1. 'Atropine-resistant' secretion of saliva in response to parasympathetic stimulation may reflect antidromic activation of sensory nerve fibres. In this investigation, the effect of pretreatment in the rat with capsaicin (total dose of 125 mg kg-1, s.c.), was determined. 2. In the parotid glands substance P (SP)/calcitonin gene-related peptide (CGRP)-containing nerve fibres around ducts and blood vessels disappeared after capsaicin, while periacinar SP-containing fibres (devoid of CGRP) and CGRP-containing fibres (devoid of SP) remained. Vasoactive intestinal peptide (VIP)-containing nerve fibres seemed to be unaffected. The parotid content of SP and CGRP was reduced by 11 and 36% respectively, while that of VIP remained unchanged. 3. The weights of the parotid glands and their sensitivity to the secretagogues methacholine and SP, injected intravenously, were unchanged as was the response to stimulation of the auriculo-temporal nerve in the presence and absence of atropine. 4. In contrast to capsaicin pretreatment, parasympathetic denervation of the parotid gland reduced the weight of the gland and produced an increase in the response to methacholine and SP. 5. For comparison, the effectiveness of the capsaicin treatment on neuropeptide content was determined in the urinary bladder. The bladder of capsaicin-pretreated rats increased in weight (21%) and in VIP content (31%), while the content of SP and CGRP was reduced by 86 and 94%, respectively. SP- and CGRP-containing nerve fibres were virtually eliminated, while VIP-containing nerve fibres seemed unaffected. 6. In conclusion, antidromic activation of primary afferent (capsaicin-sensitive) C-fibres does not contribute significantly to the 'atropine-resistant' secretory response of the parotid gland to stimulation of the parasympathetic nerve.     

Effects of yohimbine on submaxillary salivation in dogs.

1. The effects of yohimbine (0.5 mg kg-1 i.v.) on both resting and parasympathetic and sympathetic stimulation-induced submaxillary salivary responses were investigated in the anaesthetized dog. 2. Salivary secretion was increased significantly for a period of 45 min following an injection of yohimbine. 3. Sectioning of the chorda tympani (but not the cervical sympathetic) nerve abolished the yohimbine-induced increase in resting salivary secretion and potentiated that elicited by electrical stimulation of the chorda tympani nerve. 4. These results show that yohimbine increases submaxillary secretion by inhibition of presynaptic alpha 2-adrenoceptors located on the chorda tympani, which inhibit cholinergic transmission.     

Effects of atrial natriuretic peptide on adrenergically induced norepinephrine release and vasoconstriction in the dog kidney.

The effects of atrial natriuretic peptide (ANP) on the neural control of renal blood flow were examined in anesthetized dogs. Intrarenal arterial infusion of ANP (alpha-hANP, 10 and 50 ng/kg per min) suppressed the decrease in renal blood flow but not the increase in renal venous plasma norepinephrine concentration induced by renal nerve stimulation (1 and 2 Hz, for 1 min). ANP also attenuated the blood flow response to intrarenal arterial injection of methoxamine (5-20 micrograms). These results suggest that ANP acts at a postsynaptic site to suppress adrenergically induced vasoconstriction in the dog kidney.     

The pharmacology of salivary myoepithelial cells in dogs

1. Pressure changes in the submaxillary and parotid ducts of dogs, induced by nerve stimulation or intravenous injection of drugs, were studied.2. Pressure rises could be elicited by parasympathetic stimulation and by acetylcholine and methacholine, even when no secretion was evoked. These effects were abolished by atropine.3. Similarly, sympathetic stimulation, adrenaline, noradrenaline and phenylephrine raised the pressure in both glands, also in the absence of secretion. Dihydroergotamine abolished these effects. Isoprenaline increased the pressure in the submaxillary duct, but only when it caused secretion. This effect was abolished by propranolol. In the parotid gland isoprenaline caused neither secretion nor pressure rise. It is concluded that the myoepithelial cells of the two glands are supplied with alpha-adrenoceptors.4. Doses of histamine, bradykinin, kallidin and physalaemin which caused no salivary secretion raised the duct pressure even when dihydroergotamine, propranolol and atropine had been given.5. Angiotensin and 5-hydroxytryptamine increased the pressure only in some experiments. Oxytocin caused very little or no pressure rise. Vasopressin had no effect of its own but reduced the pressure raising effects of nerve stimulation or drugs.     

Lack of nitric oxide-mediated regulation of amylase secretion stimulated by VIP in parotid glands of NOD mice

The non-obese diabetic (NOD) mouse is chosen among other experimental models to study autoimmune sialadenitis resembling Sj?gren's syndrome (SS), because of its unique characteristic of developing salivary dysfunction. Based on the deep loss of nitric oxide synthase (NOS) activity in parotid glands of NOD mice observed from early stages of disease and the inhibitory effect of nitric oxide (NO) donors on amylase secretion in normal salivary glands, our goal was to investigate whether parotid glands from NOD mice lacking NOS activity presented this regulatory mechanism of amylase secretion. We found that parotid glands from NOD mice lack nitric oxide-mediated regulation of amylase secretion in response to VIP stimulation. The lack of regulation might be assigned to the loss of NOS activity as derived from the results with NOS inhibitors and increasing concentrations of VIP. These functional differences observed in NOD vs. BALB/c parotid glands occur in the absence of immune infiltrates in exocrine tissue, and it is not related to cAMP accumulation. NO-mediated regulation of amylase secretion was not observed in BALB/c submandibular glands to the same extent as described in parotid glands and was absent in submandibular glands of NOD mice.     

Potentiation of isoproterenol-induced salivation by labetalol

The authors previously reported that low doses of labetalol potentiated isoproterenol (ISO)-induced salivation in mice. The present study was carried out to ascertain the potentiating effect of labetalol in in vitro experiments using rat parotid tissue slices and their isolated cells. ISO-induced amylase release was enhanced by low concentrations of labetalol (less than 10(-6) M), while it was inhibited by high doses (more than 10(-5) M). This potentiating effect of labetalol did not occur in the Ca-free medium used for incubation or in experiments using the dispersed parotid cells or the parotid tissues which were obtained from 6-hydroxy-dopamine- or reserpine-treated rats. The effect of ISO on cyclic AMP accumulation in parotid tissue was completely blocked by the addition of labetalol in concentrations which were sufficient to increase the ISO-induced amylase release. Labetalol also inhibited the ISO-induced reduction of potassium release in parotid tissue. From these results, it is concluded that increases in the secretion of amylase and potassium from salivary glands due to the stimulation of glandular alpha-adrenoceptors by endogenous norepinephrine may play an important role in the potentiating effect of labetalol on ISO-induced salivation in mice.     

Morphine depression and tolerance of nerve-induced parotid secretion.

1 The nerve-induced secretion produced by the rat parotid gland is proportional to the frequency of stimulation. Morphine decreased the flow rate during stimulation at 2.5 and 5 Hz, but not at 20 Hz. This frequency-dependent action of morphine and was partially reversed by naloxone. 2 The secretion produced by the rat parotid gland during an intravenous infusion of acetylcholine was not diminished by morphine. Therefore, the action of morphine on nerve-induced secretion is most probably on the motor nerve terminals, which release acetylcholine. 3 Animals that had been implanted with morphine base pellets tolerated 4 times as much morphine as controls; after 6 days the minute ventilation was less depressed by graded doses of morphine than non-implanted controls. 4 Nerve-induced secretion in morphine-implanted animals was less depressed by morphine than control animals 6 and 24 h after the pellets were removed. The flow rates in the 6 h group treated with morphine were greater after naloxone than control (precipitated withdrawal) but at 24 h when withdrawal symptoms were no longer evident, naloxone produced only a slight reversal.     

Effects of endothelin-1 on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.

The effects of endothelin-1 (ET-1) on renal function and norepinephrine (NE) overflow induced by renal nerve stimulation (RNS) were examined in anesthetized dogs, and comparisons were made with effects of Bay K 8644, a calcium channel agonist. RNS at a low frequency (0.5-2.0 Hz) produced significant decreases in urine flow and urinary excretion of sodium and increased NE secretion rates without influencing renal hemodynamics. RNS, at a high frequency of 2.5-5.0 Hz which diminishes renal hemodynamics, affected urine formation and NE secretion rate more potently than did low-frequency RNS. Intrarenal arterial infusion of ET-1 (1.0 ng/kg/min) decreased the baseline level of renal blood flow by 25% and that of urinary excretion of sodium by 54-69% but did not alter basal levels of NE secretion rate. During ET-1 infusion, low-frequency RNS-induced antidiuresis was observed to an extent similar to that seen without ET-1 infusion, whereas increase in NE secretion rate elicited by RNS was significantly inhibited by ET-1 infusion (45-65% of the values without ET-1 infusion). In addition, in the case of high-frequency RNS, ET-1 did not affect antidiuretic responses but did inhibit the increase in NE secretion rate by approximately 55%. In contrast, alterations in renal excretory responses and NE secretion rate elicited by RNS were not influenced by Bay K 8644 infusion (1.0 micrograms/kg/min), a dose that decreased renal blood flow to the same degree as did 1.0 ng/kg/min of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prophylactic Effects Of Pilocarpine Hydrochloride On Xerostomia Models Induced By X-Ray Irradiation In Rats

1. In the present study, we investigated the prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by either single (15 Gy) or repeated (8.6 Gy x3 days) X-ray irradiation in rats. Pilocarpine hydrochloride was administered orally 90 min before each irradiation session. Then, 7 days later, salivary volume, amylase activity and protein concentration in the saliva secreted from the right parotid gland were measured before and after a subsequent administration of pilocarpine hydrochloride (intraduodenal). 2. In irradiated no-pretreatment rats, irradiation induced a significant reduction in both spontaneous and pilocarpine hydrochloride-stimulated secretion (both total salivary volume and flow rate), regardless of the protocol used for X-ray exposure. In irradiated, pilocarpine hydrochloride-pretreated rats, salivary secretion was increased after stimulation by pilocarpine hydrochloride (intraduodenal) to a degree that depended on the pretreatment dose of pilocarpine hydrochloride (p.o.) in both xerostomia models. 3. There were no differences in amylase or protein concentrations between irradiated rats pretreated with pilocarpine hydrochloride and irradiated no-pretreatment control rats. 4. A decrease in the weight of the parotid gland was observed in rats exposed to either the single dose or repeated irradiation protocols. Changes in the submandibular gland were less marked than those in the parotid gland. These changes in gland weight were not affected by pilocarpine hydrochloride pretreatment. 5. The responsiveness of the parotid gland to subsequent stimulation with pilocarpine hydrochloride was apparently preserved in both xerostomia models by pretreatment with pilocarpine hydrochloride, which itself increased salivary secretion. This suggests that pilocarpine hydrochloride may exert functional protective effects against xerostomia that occurs following irradiation therapy through a stimulation of salivary secretion.     

Effects of arterial hypoxemia and splenic nerve stimulation on myocardial adenosine 3',5'-Monophosphate in dogs.

Epinephrine infusion, 5-percent oxygen breathing, and splenic nerve stimulation were employed to increase cardiac output by 50-100% in anesthetized dogs. Epinephrine infusion as expected, increased plasma and myocardial cyclic AMP concentrations. Arterial hypoxemia increased cyclic AMP concentration in plasma but not in the heart. Practolol pretreatment abolished the increase in plasma cyclic AMP concentration and reduced the rise in cardiac output during hypoxemia. Splenic nerve stimulation was not associated with increases in either plasma or myocardial cyclic AMP. Adenylate cyclase activity was increased by addition of plasma into the incubation medium. However, splenic venous plasma obtained during splenic nerve stimulation did not increase adenylate cyclase activity more than control plasma obtained before stimulation. We conclude that the positive inotropic action of arterial hypoxemia and splenic nerve stimulation does not depend on the adenylate cyclase-cyclic AMP system.     

Proteinase-activated receptor-2 (PAR-2): regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice

Proteinase-activated receptor-2 (PAR-2) is expressed throughout the gastrointestinal tract including the pancreas, and may be involved in digestive functions. The aim of our study was to evaluate a potential role for PAR-2 in regulating salivary and pancreatic exocrine secretion in vivo. PAR-2-activating peptides (PAR-2-APs), but not selective PAR-1-APs, administered intravenously, increased salivary secretion in the mouse or rat; this effect of the PAR-2-APs was unaffected by atropine, phentolamine, propranolol or indomethacin. Secretion (amylase) by rat parotid gland slices in vitro was also stimulated by PAR-2-APs and trypsin, but not by activation of other PARs. PAR-2-APs, administered to rats in vivo, caused a prompt effect on pancreatic exocrine secretion. PAR-2 mRNA, known to be present in pancreatic tissue, was also detected in parotid tissue. Our results indicate that in addition to a potential role in regulating cardiovascular and respiratory functions, PAR-2 may also play a general role in vivo for the direct regulation of glandular exocrine secretion.