Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were designed to determine whether cannabinoids affect salivary gland function. For this purpose, the effect of anandamide on cAMP accumulation, amylase release and Na+-K+-ATPase activity was studied in rat parotid glands. Anandamide induced a concentration-dependent increase in cAMP and led to amylase release but inhibited Na+-K+-ATPase activity. These effects were blocked by the CB1 cannabinoid receptor antagonist, AM281. The inhibition of adenylyl cyclase activity by SQ 22536 impaired amylase release and Na+-K+-ATPase inhibition. The effect of anandamide on cAMP accumulation significantly correlated with its action either on amylase release or on Na+-K+-ATPase activity. Such correlation strongly supports the view that the effect of anandamide on amylase release and Na+-K+-ATPase activity is the result of cAMP accumulation. The relative potencies of the CB1 cannabinoid receptor antagonist, AM281, to block these three functional responses were similar, supporting the view that anandamide actions in parotid glands were achieved through a single receptor subtype, the CB1. Binding studies using the selective cannabinoid CB1 receptor antagonist, [3H]SR141716A, indicated the presence of the specific binding site. It may be concluded that in parotid glands the endogenous cannabinoid anandamide, bound to the CB1 cannabinoid receptor subtype, induces cAMP accumulation which in turn leads to amylase release and Na+-K+-ATPase inhibition.
 ...
PMID:Expression and biological effects of CB1 cannabinoid receptor in rat parotid gland. 1545 Sep 42

In the present study, we examined whether cannabinoid receptor expression and the effects of receptor stimulation vary as a function of gonadal status in a peripheral tissue, namely the male rat parotid gland. Four groups of male rats were studied: gonadal intact, castrated, castrated testosterone (1 mg/100 g bodyweight) treated and gonadal intact testosterone treated. 2. The results showed that the density of CB(1) receptors decreased after castration and that receptor density was restored to control values after testosterone treatment. This decrement was associated with a decrease of anandamide (10(-10) to 10(-5) mol/L)-induced cAMP accumulation and amylase release without changes in the anandamide-induced inhibition of Na(+)/K(+)-ATPase activity. 3. Castration did not modify either the subtype of cannabinoid receptor involved in the actions of anandamide or drug affinity for the receptor. 4. The mechanism underlying anandamide-induced cAMP accumulation, amylase release and inhibition of Na(+)/K(+)-ATPase activity, namely through the activation of adenylyl cyclase, was the same in control and castrated rats. 5. Basal cAMP accumulation, amylase release and Na(+)/K(+)-ATPase activity were not altered by castration. 6. Castration had no effect on the concentration of total protein. 7. It can be concluded that CB(1) cannabinoid receptor expression is regulated by testosterone in male rat parotid gland and this has functional implications for cAMP accumulation and amylase release.
 ...
PMID:Effects of castration on cannabinoid cb receptor expression and on the biological actions of cannabinoid in the parotid gland. 1648 71

The endocannabinoid system has been shown to mediate beneficial effects on gastrointestinal inflammation via cannabinoid receptors 1 (CB(1)) and 2 (CB(2)). These receptors have also been reported to activate the MAP kinases p38 and c-Jun NH(2)-terminal kinase (JNK), which are involved in early acinar events leading to acute pancreatitis and induction of proinflammatory cytokines. Our aim was to examine the role of cannabinoid receptor activation in an experimental model of acute pancreatitis and the potential involvement of MAP kinases. Cerulein pancreatitis was induced in wild-type, CB(1)-/-, and MK2-/- mice pretreated with selective cannabinoid receptor agonists or antagonists. Severity of pancreatitis was determined by serum amylase and IL-6 levels, intracellular activation of pancreatic trypsinogen, lung myeloperoxidase activity, pancreatic edema, and histological examinations. Pancreatic lysates were investigated by Western blotting using phospho-specific antibodies against p38 and JNK. Quantitative PCR data, Western blotting experiments, and immunohistochemistry clearly show that CB(1) and CB(2) are expressed in mouse pancreatic acini. During acute pancreatitis, an upregulation especially of CB(2) on apoptotic cells occurred. The unselective CB(1)/CB(2) agonist HU210 ameliorated pancreatitis in wild-type and CB(1)-/- mice, indicating that this effect is mediated by CB(2). Furthermore, blockade of CB(2), not CB(1), with selective antagonists engraved pathology. Stimulation with a selective CB(2) agonist attenuated acute pancreatitis and an increased activation of p38 was observed in the acini. With use of MK2-/- mice, it could be demonstrated that this attenuation is dependent on MK2. Hence, using the MK2-/- mouse model we reveal a novel CB(2)-activated and MAP kinase-dependent pathway that modulates cytokine expression and reduces pancreatic injury and affiliated complications.
 ...
PMID:Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms. 2313 24

Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.
 ...
PMID:Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells. 2743 73