TY - JOUR
T1 - Cannabinoid receptors in submandibular acinar cells
T2 - functional coupling between saliva fluid and electrolytes secretion and Ca2+ signalling
AU - Kopach, Olga
AU - Vats, Juliana
AU - Netsyk, Olga
AU - Voitenko, Nana
AU - Irving, Andrew
AU - Fedirko, Nataliya
PY - 2012/4/15
Y1 - 2012/4/15
N2 - Cannabinoid receptors (CBRs) belong to the G protein-coupled receptor superfamily, and activation of CBRs in salivary cells inhibits agonist-stimulated salivation and modifies saliva content. However, the role of different CBR subtypes in acinar cell physiology and in intracellular signalling remains unclear. Here, we uncover functional CB(1)Rs and CB(2)Rs in acinar cells of rat submandibular gland and their essential role in saliva secretion. Pharmacological activation of CB(1)Rs and CB(2)Rs in the submandibular gland suppressed saliva outflow and modified saliva content produced by the submandibular gland in vivo. Using Na+-selective microelectrodes to record secretory Na+ responses in the lumen of acini, we observed a reduction in Na+ transport following the activation of CBRs, which was counteracted by the selective CB1R antagonist AM251. In addition, activation of CB(1)Rs or CB(2)Rs caused inhibition of Na+-K+-ATPase activity in microsomes derived from the gland tissue as well as in isolated acinar cells. Using a Ca2+ imaging technique, we showed that activation of CB(1)Rs and CB(2)Rs alters [Ca2+](cyt) signalling in acinar cells by distinct pathways, involving Ca2+ release from the endoplasmic reticulum (ER) and store-operated Ca2+ entry (SOCE), respectively. Our data demonstrate the expression of CB(1)Rs and CB(2)Rs in acinar cells, and their involvement in the regulation of salivary gland functioning.
AB - Cannabinoid receptors (CBRs) belong to the G protein-coupled receptor superfamily, and activation of CBRs in salivary cells inhibits agonist-stimulated salivation and modifies saliva content. However, the role of different CBR subtypes in acinar cell physiology and in intracellular signalling remains unclear. Here, we uncover functional CB(1)Rs and CB(2)Rs in acinar cells of rat submandibular gland and their essential role in saliva secretion. Pharmacological activation of CB(1)Rs and CB(2)Rs in the submandibular gland suppressed saliva outflow and modified saliva content produced by the submandibular gland in vivo. Using Na+-selective microelectrodes to record secretory Na+ responses in the lumen of acini, we observed a reduction in Na+ transport following the activation of CBRs, which was counteracted by the selective CB1R antagonist AM251. In addition, activation of CB(1)Rs or CB(2)Rs caused inhibition of Na+-K+-ATPase activity in microsomes derived from the gland tissue as well as in isolated acinar cells. Using a Ca2+ imaging technique, we showed that activation of CB(1)Rs and CB(2)Rs alters [Ca2+](cyt) signalling in acinar cells by distinct pathways, involving Ca2+ release from the endoplasmic reticulum (ER) and store-operated Ca2+ entry (SOCE), respectively. Our data demonstrate the expression of CB(1)Rs and CB(2)Rs in acinar cells, and their involvement in the regulation of salivary gland functioning.
U2 - 10.1242/jcs.088930
DO - 10.1242/jcs.088930
M3 - Article
C2 - 22366450
SN - 0021-9533
VL - 125
SP - 1884
EP - 1895
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 8
ER -