Endocannabinoids as autoregulatory signaling molecules: coupling to nitric oxide and a possible association with the relaxation response.
Endocannabinoid signaling processes are present in diverse organisms and in organisms 500 million years divergent in evolution. Cannabinoid receptor-1 expression (CB1), anandamide, and anandamide amidase have been found in invertebrates. Furthermore, this signaling system is coupled to constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO) release in both vertebrates and invertebrates, thereby regulating neural, immune, and vascular-like functions in these divergent organisms. In human endothelial cells from various blood vessels, CB1 immunoreactive components are present as is its coupling to anandamide-stimulated cNOS-derived NO production, which exerts an autoregulatory role on cNOS release. The modulation of vascular diameter and vascular tone represents a crucial point of interest in these pathways, and interactions between NO and the sympathetic nerve system are of importance, i.e, norepinephrine. Here, a possible association of NO and endocannabinoid signaling with the relaxation response, a physiological counterpart of the stress response, may exist.
Stefano
George B
GB
The Mind/Body Medical Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. gstefano@sunynri.org
Esch
Tobias
T
Cadet
Patrick
P
Zhu
Wei
W
Mantione
Kirk
K
Benson
Herbert
H
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D019143:Evolution, Molecular; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009126:Muscle Relaxation / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated; D011955:Receptors, Drug; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase