Atropine‐resistant Secretory Responses of the Ovine Parotid Gland to Reflex and Direct Parasympathetic Stimulation

Reid, Anna-Mari; Titchen, D. A.

doi:10.1113/expphysiol.1988.sp003157

Cited by 26 publications

(17 citation statements)

References 14 publications

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“…Spirocerca lupi parasitic nodules result in local distension of the oesophageal wall and even partial obstruction of the oesophagus in more advanced cases, which may stimulate the low-threshold mechanoreceptors of the vagal afferent system and thus cause the sialorrhoea. These nodules can also result in oesophageal mucosal irritation, inflammation and pain, which would stimulate the splanchnic receptors, resulting in sialorrhoea from higher CNS centres (Kay & Phillipson 1959;Reid & Titchen 1988). Increased amounts of foamy saliva in both the oesophagus and the stomach were found in all 13 prospective sialorrhoea cases, confirming that the increased amount of saliva was a consequence of increased salivation and not the patient's inability to swallow.…”

Section: Discussionsupporting

confidence: 63%

Salivary gland enlargement and sialorrhoea in dogs with spirocercosis: A retrospective and prospective study of 298 cases

Merwe

Christie

Clift

et al. 2012

J. S. Afr. Vet. Assoc.

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This longitudinal cross-sectional clinical study investigated the incidence of sialorrhoea in dogs with spirocercosis and determined whether breed, body weight and the extent of the oesophageal involvement was associated with this presentation. A retrospective analysis was performed on the medical records of 233 dogs and information pertaining to 65 dogs was collected as part of a prospective study. All the animals were client-owned. Patients from the retrospective study underwent thoracic radiography or oesophageal endoscopy to diagnose and characterise the infection and were placed on therapy with a macrocyclic lactone, whereas the patients in the prospective study had both radiography and endoscopy routinely performed and biopsies of the oesophageal nodules collected where possible. Tru-cut biopsies of affected salivary glands were taken in 10 of 13 patients demonstrating clinical signs of sialorrhoea and salivary gland enlargement. The entire salivary gland was sectioned in an additional three dogs with spirocercosis and no sialorrhoea that were presented for post mortem examination. Sialorrhoea was present in 33/298 cases (11%). Fox terrier breeds were over-represented in the patients with sialorrhoea, comprising 36% of cases, whereas they only comprised 1.5% of the patients without sialorrhoea (p < 0.001, chi squared test) and 5% of the combined group. Dogs weighing 12 kg or less were significantly over-represented in the sialorrhoea group, 69% versus 19.5% (p < 0.001, chi square test). Age was not significantly different between the two groups (p < 0.08, Mann-Whitney test). The number of oesophageal nodules per case was significantly higher in the non-sialorrhoea cases (p = 0.048, Mann-Whitney test). The prevalence of distal oesophageal and lower oesophageal sphincter involvement, and neoplastic transformation of the nodules were not statistically different between the two groups. None of the fox terriers in either group showed neoplastic transformation of the parasitic nodules even though they were over-represented as a breed. Mandibular salivary glands were affected in 86% of cases showing sialorrhoea. Histopathology revealed acinar hyperplasia in all cases with concurrent necrosis detected in only two cases.Sialorrhoea and salivary gland enlargement has an incidence of 11% (33/298 cases) in canine spirocercosis. Small breeds (≤ 12 kg) and particularly fox terrier breeds are over-represented in the group demonstrating sialorrhoea and this appeared to be the only risk factor.The conclusion was that sialorrhoea secondary to canine spirocercosis occurs frequently and its presence should prompt further investigation for oesophageal and gastro-intestinal disease. Severely affected patients can be managed with phenobarbitone to control the dysphagia in addition to the routine macrocyclic lactones treatment.

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Section: Discussionsupporting

confidence: 63%

Salivary gland enlargement and sialorrhoea in dogs with spirocercosis: A retrospective and prospective study of 298 cases

Merwe

Christie

Clift

et al. 2012

J. S. Afr. Vet. Assoc.

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“…Earlier reports describe a non-adrenergic, non-cholinergic mediated fluid secretion (3, 20 -24). In sheep, electrical stimulation of the parotid parasympathetic nerve in the presence of atropine produced a significant increase in the flow rate (25). The authors concluded that the flow rate was produced by vasoactive intestinal peptide (VIP) release (25), however this seems unlikely since VIP receptor activation is linked to an increase in cAMP, not [Ca 2ϩ ] i .…”

Section: Discussionmentioning

confidence: 92%

“…In sheep, electrical stimulation of the parotid parasympathetic nerve in the presence of atropine produced a significant increase in the flow rate (25). The authors concluded that the flow rate was produced by vasoactive intestinal peptide (VIP) release (25), however this seems unlikely since VIP receptor activation is linked to an increase in cAMP, not [Ca 2ϩ ] i . Indeed, Ekstrom et al (26) reported that VIP treatment caused little to no fluid secretion in feline parotid glands.…”

Section: Discussionmentioning

confidence: 92%

Purinergic P2X7 Receptors Mediate ATP-induced Saliva Secretion by the Mouse Submandibular Gland

Nakamoto

Brown

Catalán

et al. 2009

Journal of Biological Chemistry

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Salivary glands express multiple isoforms of P2X and P2Y nucleotide receptors, but their in vivo physiological roles are unclear. P2 receptor agonists induced salivation in an ex vivo submandibular gland preparation. The nucleotide selectivity sequence of the secretion response was BzATP Ͼ Ͼ ATP > ADP Ͼ Ͼ UTP, and removal of external Ca 2؉ dramatically suppressed the initial ATP-induced fluid secretion (ϳ85%). Together, these results suggested that P2X receptors are the major purinergic receptor subfamily involved in the fluid secretion process. Mice with targeted disruption of the P2X 7 gene were used to evaluate the role of the P2X 7 receptor in nucleotide-evoked fluid secretion. P2X 7 receptor protein and BzATPactivated inward cation currents were absent, and importantly, purinergic receptor agonist-stimulated salivation was suppressed by more than 70% in submandibular glands from P2X 7 -null mice. Consistent with these observations, the ATP-induced increases in [Ca 2؉ ] i were nearly abolished in P2X 7 ؊/؊ submandibular acinar and duct cells. ATP appeared to also act through the P2X 7 receptor to inhibit muscarinic-induced fluid secretion. These results demonstrate that the ATP-sensitive P2X 7 receptor regulates fluid secretion in the mouse submandibular gland.Salivation is a Ca 2ϩ -dependent process (1, 2) primarily associated with the neurotransmitters norepinephrine and acetylcholine, release of which stimulates ␣-adrenergic and muscarinic receptors, respectively. Both types of receptors are coupled to G proteins that activate phospholipase C␤ (PLC␤) during salivary gland stimulation. PLC␤ activation cleaves phosphatidylinositol 1,4-bisphosphate resulting in diacylglycerol and inositol 1,4,5-trisphosphate (InsP 3 ) production. Activation of Ca 2ϩ -selective InsP 3 receptor channels localized to the endoplasmic reticulum of salivary acinar cells increases the intracellular free calcium concentration ([Ca 2ϩ ] i ). 4 Depletion of the endoplasmic reticulum Ca 2ϩ pool triggers extracellular Ca 2ϩ influx and a sustained elevation in [Ca 2ϩ ] i . This increase in [Ca 2ϩ ] i activates Ca 2ϩ -dependent K ϩ and Cl Ϫ channels promoting Cl Ϫ secretion across the apical membrane and a lumen negative, electrochemical gradient that supports Na ϩ efflux into the lumen. The accumulation of NaCl creates an osmotic gradient which drives water movement into the lumen, thus generating isotonic primary saliva. This primary fluid is then modified by the ductal system, which reabsorbs NaCl and secretes KHCO 3 producing a final saliva that is hypotonic (1, 2).Salivation also has a non-cholinergic, non-adrenergic component, the origin of which is unclear (3). In addition to muscarinic and ␣-adrenergic receptors, salivary acinar cells express other receptors that are coupled to an increase in [Ca 2ϩ ] i such as purinergic P2 and substance P receptors. Like muscarinic and ␣-adrenergic receptors, P2 receptor activation leads to a sustained increase in [Ca 2ϩ ] i in salivary acinar cells (4). In contrast, substance P receptor ac...

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“…Bethanechol infused into each carotid artery at 100 ,ug/min caused similar increases in flow and protein composition of the parotid The possibility is raised that there is a non-cholinergic parasympathetic mobilization of protein in parotid secretion of sheep. One mediator of such an effect may be vasoactive intestinal polypeptide (VIP) which has been shown to stimulate increases in flow and protein in the parotid of the sheep (Reid & Titchen, 1985) and which in the present experiments still exerted such an effect after atropine. VIP has been demonstrated in the parotid of the sheep (Harrison & Wathuta, 1980) but it is not known whether it is in association with parasympathetic nerve fibres, from which a muscarinic cholinergic release of VIP has been postulated (Fahrenkrug, Galbo, Holst & Schaffalitzky de Muckadell, 1978) in the pig.…”

Section: Ph Ysiological Society Sepltember 19815mentioning

confidence: 49%

Proceedings of the Physiological Society, 12‐14 September 1985, Cambridge Meeting: Communications

1986

The Journal of Physiology

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The effects of intravenous infusion of arginine vasopressin (AVP) are buffered by baroreceptor reflexes on which a central potentiating action of AVP is postulated (Matsuguchi & Schmid, 1982). This corresponds with the finding that AVP elicits a greater baroreceptor response for a given pressor stimulus than other vasoconstrictor agents. In our study we examined the effect on carotid sinus baroreflex sensitivity of infusing AVP at a dosage likely to result in plasma AVP levels within the normal daily range.Six healthy male volunteers (21-25 yr) attended the laboratory on two separate occasions. Institutional ethics committee approval was obtained and each subject gave written informed consent. Endogenous AVP secretion was suppressed by drinking 1-5 1 of water. This water load was maintained for the duration of the experiment by drinking water equal in volume to the amount of urine collected, usually at 20 min intervals. After ninety minutes of water loading, either synthetic AVP (5 pg kg-' min-') in 5 % dextrose or dextrose alone was infused intravenously.Infusions were administered in random order. One hour after the start of infusion, transmural pressure in the carotid sinus was increased by brief bursts of neck suction at -20, -30, -40 and -50 mmHg using the method described by Eckberg, Cavanaugh, Mark & Abboud (1975). The resultant bradycardia (prolongation of R-R interval of ECG) was plotted against the change in carotid sinus pressure to give a baroreflex function curve.Infusion of AVP caused a mean fall in urine flow rate from 13l9 to 1X3 ml min-(P < 0-001) and an increase in mean urine osmolality from 68 to 656 mosmole kg-' H20 (P < 0001). Mean prolongation of the R-R interval at each suction level did not differ significantly as a result of AVP infusion. Accordingly, the slope of the baroreflex function curve, an index of baroreflex sensitivity, is unchanged by AVP infusion at this dosage (-14-1 ms mmHg-' vs. -133 ms mmHg-', P > 0 8). There was no change in mean resting heart rate between test and control days (57 vs. 59 beats min', P > 0 4).Based on the changes observed in urine osmolality, the levels of plasma AVP in our subjects were likely to lie in the daily physiological range (Robertson, Shelton & Athar, 1976). In this range carotid sinus baroreflex sensitivity appeared to be unaltered by plasma AVP.

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Atropine‐resistant Secretory Responses of the Ovine Parotid Gland to Reflex and Direct Parasympathetic Stimulation

Cited by 26 publications

References 14 publications

Salivary gland enlargement and sialorrhoea in dogs with spirocercosis: A retrospective and prospective study of 298 cases

Salivary gland enlargement and sialorrhoea in dogs with spirocercosis: A retrospective and prospective study of 298 cases

Purinergic P2X7 Receptors Mediate ATP-induced Saliva Secretion by the Mouse Submandibular Gland

Proceedings of the Physiological Society, 12‐14 September 1985, Cambridge Meeting: Communications

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