On the type of receptor involved in the inhibitory action of adenosine at the neuromuscular junction

Abstract

The effects of adenosine and adenosine analogues (1‐N6‐phenylisopropyladenosine (1‐PIA), d‐N6‐phenylisopropyladenosine (d‐PIA), N6‐cyclohexyladenosine (CHA), N6‐methyladenosine, 5′‐N‐ethyl‐carboxamide adenosine (NECA) and 2‐chloroadenosine) on evoked endplate potentials (e.p.ps) and on twitch tension were investigated in innervated sartorius muscles of the frog. Adenosine and its analogues decreased, in a concentration‐dependent manner, the amplitude of both the e.p.ps and the twitch responses evoked by indirect stimulation. The order of potencies in decreasing twitch tension was: 1‐PIA, CHA, NECA > 2‐chloroadenosine > d‐PIA > n6‐methyladenosine, adenosine. 1‐PIA was about ten fold more potent than d‐PIA. None of the adenosine analogues tested affected the twitch responses of directly stimulated tubocurarine‐paralyzed muscles. In concentrations that did not modify neuromuscular transmission, theophylline and 8‐phenylth‐eophylline (8‐PT) but not isobutylmethylxanthine (IBMX), antagonized the inhibitory action of 2‐chloroadenosine at the neuromuscular junction. 8‐PT behaved as a competitive antagonist and was about forty fold more potent than theophylline. It is concluded that the R‐type adenosine receptor at the neuromuscular junction should not be classified in the A1/A2 system. The possibility of calcium‐linked adenosine receptors having pharmacological profiles distinct from those originally defined as modulating adenylate cyclase is discussed. 1985 British Pharmacological Society