Rat salivary gland ligation causes reversible secretory hypofunction

Abstract

Aim: To determine the influence of inflammation on salivary secretion. Secretion by salivary glands involves interactions between nerves, blood vessels and salivary cells. The present study investigated the effects of inflammation on rat submandibular gland function following acute ductal obstruction. Methods: Under recovery anaesthesia a metal clip was placed on the main duct of the submandibular gland. After 24 h salivary secretion was evoked by nerve and methacholine stimulation. For recovery experiments the clip was removed after 24 h and the animal left to recover for 3 days when salivary function was again assessed. Results: By 24 h of obstruction an inflammatory infiltrate had developed within the obstructed gland and stimulated salivary flows were just 20% of the normal secretion, whilst protein secretion and ion reabsorption were also severely impaired. If ductal obstruction was removed after 24 h the salivary function returned to normal after 3 days of recovery. In vitro analysis of cells from 24-h ligated glands revealed normal changes in intracellular calcium (the main secondary messenger involved in fluid secretion) in response to methacholine stimulation. Protein secretion from isolated cells indicated some changes in particular to methacholine-induced protein secretion although a significant protein secretion was still seen in response to isoprenaline -the main stimulus for protein secretion. Conclusion: This report demonstrates reversible salivary inhibition associated with an inflammatory infiltrate within the salivary gland.

P2X7 receptor activation induces inflammatory responses in salivary gland epithelium

“…Studies (10,15,31,49,81,89) of duct-ligated salivary glands have demonstrated a progressive atrophy of acinar cells, loss of saliva flow, and infiltration of immune cells within 24 h of ligation. Results from the current study demonstrate that BzATP perfusion of the main SMG excretory duct before a 24-h duct ligation induces significant immune cell infiltration, a response mediated by the P2X7R since it is absent in SMG of P2X7R Ϫ/Ϫ mice (Fig.…”

“…The induction of acute salivary gland inflammation by ligation of the primary SMG excretory duct has been used by our group and others (2,10,15,31,49,81,89,98) for many years as an in vivo model of salivary gland dysfunction. Studies (10,15,31,49,81,89) of duct-ligated salivary glands have demonstrated a progressive atrophy of acinar cells, loss of saliva flow, and infiltration of immune cells within 24 h of ligation.…”

“…Moreover, the use of P2X7R antagonists in clinical trials for rheumatoid arthritis and inflammatory bowel disease underscores the importance of this receptor in chronic inflammatory diseases (3). To investigate the role of P2X7R activation in salivary gland inflammation in vivo, we utilized the mouse model of unilateral SMG excretory duct ligation, a commonly used model of acute salivary gland inflammation (2,10,15,31,49,81,89,98). To activate the P2X7R in vivo, 20 l of 3 mM BzATP were perfused into the main SMG excretory duct of wild-type and P2X7R Ϫ/Ϫ mice followed by duct ligation and after 24 h the glands were histologically analyzed, as described in MATE-RIALS AND METHODS.…”

Nasal IgA secretion in a murine model of acute stress. The possible role of catecholamines.

“…The influence of cholinergic and adrenergic innervation on IgA secretion has been reported at the intestinal level (Schmidt et al, 2007) and in the rat submandibular salivary gland Proctor, Carpenter et al, 2000;Proctor and Carpenter, 2002;Proctor et al, 2003a;Proctor et al, 2003b;Carpenter et al, 2004;Carpenter et al, 2005;Carpenter et al, 2007;Cox et al, 2007;Proctor and Carpenter, 2007). In the nasal mucosa, the cholinergic effect could have been enhanced by the adrenergic stimulation of the glands (Malm et al, 1983;Patow et al, 1984;Mullol et al, 1992;Morishita, 1995).…”

Endocannabinoids mediate hyposalivation induced by inflammogens in the submandibular glands and hypothalamus

“…In agreement with these results, it was described a decrease of saliva secretion in response to all types of secretagogues at early stages of inflammatory diseases. 41 Moreover, we have previously reported that endocannabinoids mediate salivary hypofunction after systemic inflammation, evaluated 3 h after of LPS injection. 28 In the present work, we evaluated the effect of LPS at shorter time (1 h) that was enough to increase TNFa glandular concentration, since the endotoxin was injected into the SMG, directly.…”