The agonists for nociceptors are ubiquitous, but the modulators are specific: P2X receptors in the sensory neurons are modulated by cannabinoids |
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Authors: | O Krishtal N Lozovaya A Fedorenko I Savelyev I Chizhmakov |
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Institution: | (1) Department of Cellular Membranology, Bogomoletz Institute of Physiology, Bogomoletz Street 4, Kiev, 01024, Ukraine |
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Abstract: | P2X2 and P2X3 receptors expressed in mammalian sensory neurons participate in nociception. Cannabinoid receptors modulate
nociceptive processing in various models of pain. They are also expressed in nociceptive sensory neurons. We have examined
the effect of cannabinoids on the slow P2X2 and P2X2/3 receptors in the cells isolated from nodosal and dorsal root ganglia
of rat. The study was carried out by means of the whole-cell patch clamp and rapid superfusion methods. We have found that
both endogenous and synthetic cannabinoids (anandamide, WIN55,212-2, and (R)-(+)-methanandamide) inhibit the slow response to ATP mediated by P2X2 and P2X2/3 receptors in a majority of tested neurons.
This inhibition was significant but only partial: anandamide (0.5–1 μM) inhibited the response to 51±21% of control. In the
remaining minority of tested neurons, the response was transiently facilitated. The effect of cannabinoids appears to be mediated
via cannabinoid CB1 receptors: it was reversibly inhibited by selective CB1 antagonist, SR141716A (10 μM). Introduction of cyclic AMP (0.5 mM) into the cell potently facilitated the inhibitory effect
of cannabinoids: the ATP-activated current was inhibited to 13±10% of control. These data indicate that cannabinoids may inhibit
nociceptive responses produced by P2X receptors. |
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Keywords: | Cannabinoids P2X receptors ATP Pain |
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