Cannabinoid and lipid-mediated vasorelaxation in retinal microvasculature

Macintyre, Jonathan; Dong, Alexander; Straiker, Alex; Zhu, Jiequan; Howlett, Susan E.; Bagher, Amina M.; Denovan‐Wright, Eileen M.; Yu, Dao‐Yi; Kelly, Melanie E. M.

doi:10.1016/j.ejphar.2014.03.055

Cited by 49 publications

(50 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are consistent with the results of studies using bovine ophthalmic arteries and mesenteric arterioles, in which cannabinoids mediated vasorelaxation via CB 1 , whereas CB 2 was not involved [17, 40]. Although several studies have demonstrated that CB e is involved in cannabinoid-induced vasodilation via an endothelium-dependent signaling mechanism [16, 41], this may be attributable to the different cannabinoids or species used in those studies. However, using an isolated retinal vessel model, MacIntyre et al reported that neither R-(+)-WIN55212-2 nor the CB 1 -selective agonist arachidonyl-2-chloroethylamide caused the dilation of precontracted retinal microvessels [16].…”

Section: Discussionsupporting

confidence: 87%

“…The pharmacological effects of cannabinoids are predominantly mediated by CB 1 , CB 2 , or CB e [15, 16, 35-39]. In our study, we have shown that R-(+)-WIN55212-2-induced vasorelaxation was suppressed by two CB 1 antagonists, but not by a CB 2 antagonist.…”

Section: Discussionmentioning

confidence: 46%

“…To test whether the R-(+)-WIN55212-2-induced vasodilatory response was dependent on the endothelium, the endothelium was chemically denuded with CHAPS (0.3%) [16]. Preincubation with CHAPS did not significantly affect the diameter of the non-precontracted capillaries ( P > 0.05 vs endothelium intact vessels) or NA-precontracted capillaries ( P > 0.05 vs endothelium-intact vessels; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have examined the regulatory effects of cannabinoids on vessel tone [8, 16, 32], although these studies focused on arteries, arterioles or isolated vessels. However, there has been no direct evidence that cannabinoids affect capillaries or pericytes.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have addressed the increasing neuroprotective and therapeutic potential of cannabinoids in systematic [11] and retinal disease [12-14], and several recent studies have evaluated the effects of cannabinoids on the ocular vascular system. Yu et al reported that abnormal cannabidiol relaxed the resistant arterioles in the retina [15, 16]. Romano et al also reported the vasorelaxing effect of anandamide and WIN55212-2 on the bovine ophthalmic artery [17].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Cannabinoids Regulate the Diameter of Pericyte-Containing Retinal Capillaries in Rats

Zong

Zhou

Cheng

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. We therefore investigated the effect of cannabinoids on retinal capillaries and pericytes. Methods: The effects of cannabinoids on capillary diameters were determined using an ex vivo whole-mount rat retinal model. Western blotting, quantitative PCR, and immunohistochemistry were performed to explore the underlying mechanism. Results: Endogenous cannabinoid 2-arachidonoylglycerol and anandamide and exogenous cannabinoid (R-(+)-WIN55212-2) dilated the noradrenaline-precontracted capillaries in a concentration-dependent manner (1 µM to 0.1 mM). The extent of vasorelaxation was positively correlated with changes in pericyte width. The effects of R-(+)-WIN55212-2 on vasorelaxation and pericyte width were inhibited by a cannabinoid receptor type-1 (CB1) antagonist, AM251 or rimonabant (SR141716A), the nitric oxide synthase inhibitor l-NAME, and the guanylate cyclase inhibitor ODQ. They were also abolished by the removal of the endothelium, but not by the cannabinoid receptor-2 antagonist SR144528, the endothelial cannabinoid receptor antagonist O-1918, or the cyclooxygenase inhibitor indomethacin. Conclusion: The exogenous cannabinoid R-(+)-WIN55212-2 promotes the vasorelaxation of pericyte-containing rat retinal capillaries. This effect of R-(+)-WIN55212-2 is dependent on CB₁ and the nitric oxide–cyclic guanosine monophosphate pathway, and requires an intact endothelium.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 46%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cannabinoids Regulate the Diameter of Pericyte-Containing Retinal Capillaries in Rats

Zong

Zhou

Cheng

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

G protein coupled receptor 18: A potential role for endocannabinoid signaling in metabolic dysfunction

Rajaraman

Simcocks

Hryciw

et al. 2015

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Endocannabinoids are products of dietary fatty acids that are modulated by an alteration in food intake levels. Overweight and obese individuals have substantially higher circulating levels of the arachidonic acid derived endocannabinoids, anandamide and 2-arachidonoyl glycerol, and show an altered pattern of cannabinoid receptor expression. These cannabinoid receptors are part of a large family of G protein coupled receptors (GPCRs). GPCRs are major therapeutic targets for various diseases within the cardiovascular, neurological, gastrointestinal, and endocrine systems, as well as metabolic disorders such as obesity and type 2 diabetes mellitus. Obesity is considered a state of chronic low-grade inflammation elicited by an immunological response. Interestingly, the newly deorphanized GPCR (GPR18), which is considered to be a putative cannabinoid receptor, is proposed to have an immunological function. In this review, the current scientific knowledge on GPR18 is explored including its localization, signaling pathways, and pharmacology. Importantly, the involvement of nutritional factors and potential dietary regulation of GPR18 and its (patho)physiological roles are described. Further research on this receptor and its regulation will enable a better understanding of the complex mechanisms of GPR18 and its potential as a novel therapeutic target for treating metabolic disorders.

show abstract

Cannabidiol Inhibits IgE‐Mediated Mast Cell Degranulation and Anaphylaxis in Mice

Yang,

Lee,

Kim

et al. 2023

Molecular Nutrition Food Res

View full text Add to dashboard Cite

ScopeCannabidiol (CBD), the most abundant non‐psychoactive constituent of the plant Cannabis sativa, is known to possess immune modulatory properties. This study investigates the effects of CBD on mast cell degranulation in human and mouse primary mast cells and passive cutaneous anaphylaxis in mice.Methods and resultsMouse bone marrow‐derived mast cells and human cord‐blood derived mast cells are generated. CBD suppressed antigen‐stimulated mast cell degranulation in a concentration‐dependent manner. Mechanistically, CBD inhibited both the phosphorylation of FcεRI downstream signaling molecules and calcium mobilization in mast cells, while exerting no effect on FcεRI expression and IgE binding to FcεRI. These suppressive effects are preserved in the mast cells that are depleted of type 1 (CB1) and type 2 (CB2) cannabinoid receptors, as well as in the presence of CB1 agonist, CB2 agonist, CB1 inverse agonist, and CB2 inverse agonist. CBD also inhibited the development of mast cells in a long‐term culture. The intraperitoneal administration of CBD suppressed passive cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and decrease in the number of degranulated mast cells.ConclusionBased on these results, the administration of CBD is a new therapeutic intervention in mast cell‐associated anaphylactic diseases.

show abstract

Cannabinoid and lipid-mediated vasorelaxation in retinal microvasculature

Cited by 49 publications

References 62 publications

Cannabinoids Regulate the Diameter of Pericyte-Containing Retinal Capillaries in Rats

Cannabinoids Regulate the Diameter of Pericyte-Containing Retinal Capillaries in Rats

G protein coupled receptor 18: A potential role for endocannabinoid signaling in metabolic dysfunction

Cannabidiol Inhibits IgE‐Mediated Mast Cell Degranulation and Anaphylaxis in Mice

Contact Info

Product

Resources

About