Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC60
Cannabinoid receptors in submandibular acinar cells: functional coupling between fluid and electrolytes secretion and Ca2+ signalling
N. Fedirko1, O. Kopach2, N. Voitenko2, A. Irving3
1. Lviv National University, Lviv, Ukraine. 2. Bogomoletz Institute of Physiology, Kiev, Ukraine. 3. University of Dundee, Dundee, United Kingdom.
Cannabinoid receptors (CBRs) belong to G protein-coupled receptor superfamily. Activation of CBRs in salivary cells inhibits agonist-stimulated salivation and modifies saliva content. The role of different CB receptor subtypes in acinar cell physiology and in their intracellular signalling remains unclear. Experiments were conducted on male Wistar rats (1-1,5 month old) after anaesthesia using i.p. injection of pentobarbital (30-40 mg/kg). In vivo studies (which lasted a maximum of 30 min) were performed to address the effect of CB1R and CB2R agonists on basal salivation by the submandibular gland. Using high-speed Na+-selective microelectrodes the secretory Na+ responses were recorded in the lumen of acini in submandibular gland tissue. Calcium imaging was utilized to detect the CBRs-induced dynamic changes of free cytosolic Ca2+ concentration ([Ca2+]cyt) in isolated acinar cells. Key results: Agonists of CB1 and CB2 receptors significantly inhibited basal saliva flow rate with concomitant increase in both total protein and calcium concentrations in unstimulated saliva secreted by the submandibular gland. Recordings of extracellular Na+ concentration ([Na+]e) in the lumen of acinus revealed a reduced Na+ transport during the activation of CBRs, which was eliminated by a selective antagonist of CB1R, AM251. In isolated acinar cells, activation of both CB1R and CB2R induced an increase in [Ca2+]cyt due to Ca2+ release from the ER or the store-operated Ca2+ entry (SOCE) respectively. Conclusions and implications: Acinar cells of rat submandibular gland possess functional CB1 and CB2 receptors that upon activation suppress basal saliva outflow and modify saliva content. CB1 and CB2 receptors trigger [Ca2+]cyt signalling in acinar cells by distinct pathways. Our data demonstrate a physiological role of endocannabinoid system for the regulation of salivary gland functioning.
Where applicable, experiments conform with Society ethical requirements