Connections between P2 purinoceptors and capsaicin-sensitive afferents in the intestine and other tissues.
Relations between P2 purinoceptors and capsaicin-sensitive sensory neurons include an excitatory action of P2 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 P2 purinoceptor agonists can activate primary afferent neurons, through P2X3 receptors and probably other purinoceptors as well, but evidence for an involvement of P2 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 P2 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 P2 purinoceptor stimulant from sensory nerves. Our data show that cholinergic contractions of the guinea-pig ileum in response to the P2 purinoceptor agonist alpha,beta-methylene ATP (alpha,beta-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 microM) are insensitive to suramin (a P2 purinoceptor antagonist; 100 microM). In the presence of antagonists acting at tachykinin NK1 and NK2 receptors, however, suramin (100 microM) causes a significant inhibition of the capsaicin-evoked contraction. These data indicate that capsaicin-sensitive nerves are not involved in the excitatory effect of alpha,beta-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.
Barthó
L
L
Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Hungary. lbartho@apacs.pote.hu
Lénárd
L
L
Lázár
Z
Z
Maggi
C A
CA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000294:innervation*; D009197:Myenteric Plexus / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D002211:Capsaicin