Connections between P 2 purinoceptors and capsaicin-sensitive afferents in the intestine and other tissues

Relations between P 2 purinoceptors and capsaicin-sensitive sensory neurons include an excitatory action of P 2 purinoceptor agonists on spinal afferent neurons, as well as release of ATP from afferents at their central and peripheral endings, and a possible participation of ATP in nociception and/or in `local efferent' responses mediated by sensory nerves at the periphery. The present paper briefly summarizes available evidence on these interrelations. Ample evidence shows that ATP and other P 2 purinoceptor agonists can activate primary afferent neurons, through P2X 3 receptors and probably other purinoceptors as well, but evidence for an involvement of P 2 purinoceptors in nociception or in `local efferent' responses due to activation of primary afferents is, at best, circumstantial. The possibility is also dealt with that P 2 purinoceptor activation may cause small intestinal contraction with the mediation of capsaicin-sensitive sensory neurons and that the motor response to capsaicin in this tissue may involve the release of a P 2 purinoceptor stimulant from sensory nerves. Our data show that cholinergic contractions of the guinea-pig ileum in response to the P 2 purinoceptor agonist α,β-methylene ATP (α,β-meATP) are blocked by atropine, but not by in vitro capsaicin pretreatment (which completely blocks the contractile action of capsaicin). Cholinergic ileum contractions due to capsaicin (2 μM) are insensitive to suramin (a P 2 purinoceptor antagonist; 100 μM). In the presence of antagonists acting at tachykinin NK 1 and NK 2 receptors, however, suramin (100 μM) causes a significant inhibition of the capsaicin-evoked contraction. These data indicate that capsaicin-sensitive nerves are not involved in the excitatory effect of α,β-methylene ATP on myenteric neurons. On the other hand, ATP is probably involved in the `non-tachykininergic' component of the capsaicin-induced excitatory response of the small intestine. ATP may originate from sensory neurons and probably acts as activator of myenteric nerves.