Delta 9-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism.
نویسندگان
چکیده
Although Delta(9)-tetrahydrocannabinol (THC) produces analgesia, its effects on nociceptive primary afferents are unknown. These neurons participate not only in pain signaling but also in the local response to tissue injury. Here, we show that THC and cannabinol induce a CB(1)/CB(2) cannabinoid receptor-independent release of calcitonin gene-related peptide from capsaicin-sensitive perivascular sensory nerves. Other psychotropic cannabinoids cannot mimic this action. The vanilloid receptor antagonist ruthenium red abolishes the responses to THC and cannabinol. However, the effect of THC on sensory nerves is intact in vanilloid receptor subtype 1 gene knock-out mice. The THC response depends on extracellular calcium but does not involve known voltage-operated calcium channels, glutamate receptors, or protein kinases A and C. These results may indicate the presence of a novel cannabinoid receptor/ion channel in the pain pathway.
منابع مشابه
Cannabinoid-mediated elevation of intracellular calcium: a structure-activity relationship.
This laboratory has reported previously that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabinol (CBN) robustly elevate intracellular calcium ([Ca(2+)](i)) in resting human and murine T cells, whereas CP55,940 [5-(1,1-dimethylheptyl)-2-(5-hydroxy-2-(3-hydroxypropyl)cyclohexyl)phenol], a high-affinity ligand for CB1 and CB2, does not. In light of our previous studies, the objective of th...
متن کاملCannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.
BACKGROUND Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammat...
متن کاملPharmacological actions of cannabinoids.
Mammalian tissues express at least two types of cannabinoid receptor, CB1 and CB2, both G protein coupled. CB1 receptors are expressed predominantly at nerve terminals where they mediate inhibition of transmitter release. CB2 receptors are found mainly on immune cells, one of their roles being to modulate cytokine release. Endogenous ligands for these receptors (endocannabinoids) also exist. Th...
متن کاملEffect of Cannabinoid Receptor Activation on Spreading Depression
Objective(s) The objective of this study was to evaluate the effect of cannabinoid on cortical spreading depression (CSD) in rat brain. Cannabis has been used for centuries for both symptomatic and prophylactic treatment of different types of headaches including migraine. CSD is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain. Materials and Methods T...
متن کاملMini - Review 11 - Nor - 9 - carboxy - ∆ 9 - tetrahydrocannabinol – a ubiquitous yet underresearched cannabinoid . A re - view of the literature
Synthetic ∆ 9 -tetrahydrocannabinol (THC), pharmaceutical grade herbal cannabis as well as formulations of well-defined cannabis extracts are available as registered medicines in several countries. It is generally accepted that the main central and peripheral pharmacological effects of THC are mediated by CB1 and CB2 cannabinoid receptors. Cytochrome P450-mediated oxidations of THC afford the n...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of neuroscience : the official journal of the Society for Neuroscience
دوره 22 11 شماره
صفحات -
تاریخ انتشار 2002