Existence Of Cannabinoid Receptors Research Articles

Activation of adipose tissue cannabinoid receptors 1 (CB1R) alters antilipolytic action of insulin and increases lipolysis in mice

Objectives: Recent data indicate that activation of peripheral endocannabinoid system (ECS) in tissues such as liver, muscle or adipose tissue may directly influence carbohydrate and lipid metabolism. The existence of cannabinoid receptors 1 (CB1R) and ECS enzymatic machinery has been demonstrated in mature adipocytes, nevertheless studies regarding their role in lipogenesis and lipolysis control are often conflicting.

The Endocannabinoids Anandamide and Virodhamine Modulate the Activity of the Candidate Cannabinoid Receptor GPR55

The role of cannabinoid receptors in inflammation has been the topic of many research endeavors. Despite this effort, to date the involvement of the endocannabinoid system (ECS) in inflammation remains obscure. The ambiguity of cannabinoid involvement may be explained by the existence of cannabinoid receptors, other than CB(1) and CB(2), or a consequence of interaction of endocannabinoids with other signaling systems. GPR55 has been proposed to be a cannabinoid receptor; however the interaction of the endocannabinoid system with GPR55 remains elusive. Consequently this study set about to examine the effects of the endocannabinoids, anandamide (AEA) and virodhamine, on GPR55 mediated signaling. Specifically, we assessed changes in β-arrestin2 (βarr2) distribution and GPR55 receptor internalization following activation by lysophosphatidylinositol (LPI), the synthetic cannabinoid ligand SR141716A, and new selective synthetic GPR55 agonists. Data obtained from the experiments presented herein demonstrate that AEA and virodhamine modulate agonist-mediated recruitment of βarr2. AEA and virodhamine act as partial agonists; enhancing the agonist effect at low concentrations and inhibiting it at high concentrations. Furthermore, both virodhamine and AEA significantly attenuated agonist-induced internalization of GPR55. These effects are attributed to the expression of GPR55, and not CB(1) and CB(2) receptors, as we have established negligible expression of CB(1) and CB(2) in these GPR55-transfected U2OS cells. The identification of select endocannabinoids as GPR55 modulators will aide in elucidating the function of GPR55 in the ECS.

INHIBITORY EFFECTS OF CANNABINOID RECEPTOR LIGANDS ON ELECTRICALLY-EVOKED RESPONSES IN RAT ISOLATED TRACHEAL RING SEGMENTS

We have examined the possible existence of cannabinoid receptors in the isolated rat tracheal ring segments by studying the effects of some cannabinoid receptor ligands on electrically-induced contractions. Anandamide (10−8–3×10−5m), an endogenous ligand for cannabinoid receptors, and WIN 55,212-2 (10−9–3×10−5m), a moderately selective CB2agonist, inhibited electrically evoked contractions of the rat tracheal ring segments in a concentration-related manner. Addition of phentolamine (10−6m) to Krebs Henseleit solution to block α2-adrenoceptors did not affect anandamide-induced inhibition of the electrically evoked contractions. The EC25(−log m) values were 5.25±0.2 and 5.8±0.4 for anandamide and WIN 55,212-2, respectively. The maximal inhibition produced by the highest concentration of the agonists used was 51.4±5.8% for anandamide and 35.1±19.5% for WIN 55,212-2. WIN 55,212-3 also produced a concentration-dependent inhibition of the electrically evoked contractions. The maximal inhibition produced by WIN 55,212-3 was 15.8±2.4. The inhibitory effects of anandamide and WIN 55,212-2 were not attenuated by SR141716A (10−6m), a selective CB1receptor antagonist. Anandamide (10−8–3×10−5m) did not relax rat tracheal ring segments pre-contracted with carbachol (10−6m). These results suggest that anandamide and WIN 55,212-2 produce pre-junctional inhibitory effects in the rat trachea and that these effects were likely mediated through cannabinoid CB2receptors. These effects were probably non-cannabinoid receptor-mediated considering the high concentrations of the agents required to produce inhibitory responses and the effectiveness of WIN 55,212-3.pc

Cannabinoids as potential new analgesics

Among other pharmacological properties analgesia is one of the important features of cannabinoids with therapeutical prospects. Cannabinoids have been shown to produce antinciciception in experimental animals and humans. Recently a new system of neuromodulation based upon the existence of cannabinoid receptors and their endogenous agonists has emerged. This has been proposed as another of the endogenous pain control systems. Current evidence indicate an interaction between cannabinoid and opioid systems, the latter being of known relevance in nociception. The fact that either exogenous or endogenous opioids enhanced cannabinoid-induced antinociception suggests simultaneous activation of both opioid and cannabinoid receptors by drugs as a new analgesic strategy.