Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation.
نویسندگان
چکیده
Recently, the cannabinoid (CB) receptor agonist anandamide (AEA) has been shown to excite perivascular terminals of primary sensory neurons via activation of the vanilloid receptor-1 (VR-1). To determine whether AEA stimulates central terminals of these neurons, via VR-1 activation, we studied the release of calcitonin gene-related peptide (CGRP)- and substance P (SP)-like immunoreactivities (LI) from slices of rat dorsal spinal cord. Mobilization of Ca(2+) in rat dorsal root ganglion (DRG) neurons in culture was also studied. AEA (0.1-10 micrometer) increased the outflow of CGRP-LI and SP-LI from slices of the rat dorsal spinal cord in a Ca(2+)-dependent manner and increased [Ca(2+)](i) in capsaicin-sensitive cultured DRG neurons. Both effects of AEA were abolished by capsaicin pretreatment and by the VR-1 antagonist capsazepine but not affected by the CB receptor antagonists AM281 or AM630. Both neuropeptide release and Ca(2+) mobilization induced by electrical field stimulation (EFS) were inhibited by a low concentration of AEA (10 nm). Inhibition by AEA of EFS-induced responses was reversed by AM281 and AM630, but was not affected by capsazepine. Results indicate that stimulation of VR-1 with high concentrations of AEA excites central terminals of capsaicin-sensitive DRG neurons, thus causing neuropeptide release in the dorsal spinal cord. This novel activity opposes the CB receptor-mediated inhibitory action of low concentrations AEA. However, only if large amounts of endogenous AEA could be produced at the level of the dorsal spinal cord, they may not inhibit, but rather activate, nociceptive sensory neurons.
منابع مشابه
Vanilloid-mediated heterosynaptic facilitation of inhibitory synaptic input to neurons of the rat dorsal motor nucleus of the vagus.
Vanilloid type-1 receptors (VR1) are abundant in the dorsal vagal complex, where their function is mostly unknown. We examined the role of VR1 in regulating synaptic inputs to neurons of the dorsal motor nucleus of the vagus (DMV). Using patch-clamp recordings from DMV neurons in brainstem slices, capsaicin was found to increase action potential-independent inhibitory input onto DMV neurons. Th...
متن کاملFunctional Expression of AMPA Receptors on Central Terminals of Rat Dorsal Root Ganglion Neurons and Presynaptic Inhibition of Glutamate Release
No direct evidence has been found for expression of functional AMPA receptors by dorsal root ganglion neurons despite immunocytochemical evidence suggesting they are present. Here we report evidence for expression of functional AMPA receptors by a subpopulation of dorsal root ganglion neurons. The AMPA receptors are most prominently located near central terminals of primary afferent fibers. AMP...
متن کامل(R)-(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)-urea (ABT-102) blocks polymodal activation of transient receptor potential vanilloid 1 receptors in vitro and heat-evoked firing of spinal dorsal horn neurons in vivo.
The transient receptor potential vanilloid (TRPV) 1 receptor, a nonselective cation channel expressed on peripheral sensory neurons and in the central nervous system, plays a key role in pain. TRPV1 receptor antagonism is a promising approach for pain management. In this report, we describe the pharmacological and functional characteristics of a structurally novel TRPV1 antagonist, (R)-(5-tert-...
متن کاملActivation of transient receptor potential ankyrin 1 induces CGRP release from spinal cord synaptosomes.
Transient receptor potential ankyrin 1 (TRPA1) is a sensor of nociceptive stimuli, expressed predominantly in a subpopulation of peptidergic sensory neurons which co-express the noxious heat-sensor transient receptor potential vanilloid 1. In this study, we describe a spinal cord synaptosome-calcitonin gene-related peptide (CGRP) release assay for examining activation of TRPA1 natively expresse...
متن کاملComparison of effects of anandamide at recombinant and endogenous rat vanilloid receptors.
BACKGROUND Anandamide, an endogenous lipid, activates both cannabinoid (CB(1)) and vanilloid (VR1) receptors, both of which are co-expressed in rat dorsal root ganglion (DRG) cells. Activation of either receptor results in analgesia but the relative contribution of CB(1) and VR1 in anandamide-induced analgesia remains controversial. Here we compare the in vitro pharmacology of recombinant and e...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of neuroscience : the official journal of the Society for Neuroscience
دوره 21 4 شماره
صفحات -
تاریخ انتشار 2001