Evidence for the presence of P 1-purinoceptors on cholinergic nerve terminals in the guinea-pig ileum

Abstract

The inhibitory effects of adenosine, ATP, 5′-adenylyl methylene diphosphonate (β, γ-meATP) and adenosine 5′-α, β-methylene triphosphonate (α, β-meATP) were compared on the cholinergic twitch responses to transmural stimulation of the guinea-pig ileum. Adenosine ATP and β, γ-meATP reduced the twitch responses in a concentration dependent manner. Theophylline antagonized and dipyridamole potentiated the inhibitory responses to adenosine, ATP and β, γ-meATP. Inhibitory responses to α, β-meATP were usually preceded by an enhancement in twitch height. Contractions of the unstimulated ileum to α, β-meATP were blocked by atropine and tetrodotoxin while those elicited by ATP were unaffected, which suggests that thetial excitatory effects of α, β-meATP may be due to its ability to release ACh from cholinergic nerve terminals. Use of high pressure liquid chromatography and bioluminescence assay techniques demonstrated the ability of the tissue to degrade ATP and β, γ-meATP and, at a much slower rate, α, β-meATP. Inhibitory responses to ATP, AMP and β, γ-meATP were reduced by adenosine deaminase, which also abolished responses to adenosine. 5′-AMP deaminase abolished responses to AMP and adenosine, and reduced those to ATP and β, γ-meATP. The results suggest that the inhibitory effect of ATP on cholinergic neurotransmission is due to its rapid breakdown to AMP or adenosine, which act on prejunctional P 1-purinoceptors.