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

Abstract

I The effects of adenosine and adenosine analogues (L-N6-phenylisopropyladenosine (L-PIA), D-N6-phenylisopropyladenosine (D-PIA), N6-cyclohexyladenosine (CHA), N6-methyladenosine, 5'-N-ethylcarboxamide 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. 2 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: L-PIA, CHA, NECA > 2-chloroadenosine> D-PIA > N6-methyladenosine, adenosine. L-PIA was about ten fold more potent than D-PIA. 3 None of the adenosine analogues tested affected the twitch responses of directly stimulated tubocurarine-paralyzed muscles. 4 In concentrations that did not modify neuromuscular transmission, theophylline and 8-phenyltheophylline (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. 5 It is concluded that the R-type adenosine receptor at the neuromuscular junction should not be classified in the A,/A2 system. The possibility of calcium-linked adenosine receptors having pharmacological profiles distinct from those originally defined as modulating adenylate cyclase is discussed.

Studies on the receptor mediating cyclic AMP‐independent enhancement by adenosine of IgE‐dependent mediator release from rat mast cells

“…These findings add weight to the growing amount of evidence that the activity of adenosine analogues in producing physiological responses do not necessarily conform to the A,/A2 classification defined using inhibition or activation of adenylate cyclase as an indicator of activity. For example, the inhibitory potencies of D-PIA and L-PIA at the frog sartorius neuromuscular junction suggest an A2-receptor-mediated effect, whereas the relative activities of other analogues suggest an A1-receptor type (Ribeiro & Sebastiao, 1985).…”

Responses of the aorta of the garter snake (Thamnophis sirtalis parietalis) to purines

“…Based on these two sets of criteria, the results from this -log (Adenosine analogue) Figure 1 Cumulative concentration-response relationships for adenosine (A, n = 13), NECA (*, n = 9), R-PIA (U, n = 7), S-PIA (0, n = 7) and 2-CA (V, n = 5) on noradrenaline (EC" concentration) identification of this receptor is confounded further if one takes into consideration the proposed existence of the A3-receptor believed to exist on nerve endings and the heart and not coupled to adenylyl cyclase. The A3-receptor has been described as having an agonist profile of cyclohexyl adenosine (CHA), R-PIA and NECA being the most potent, irrespective of their order, and more potent than 2-CA (Ribeiro & Sebastiao, 1985). The adenosine receptor of the snake aorta does not appear to fall into either P1-purinoceptor subtype, thus it could also be argued that the receptor 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) was found to be ineffective at blocking adenosine in the stomach and intestine of the stickleback (Knight & Burnstock, 1993).…”

Characterization of adenosine receptors in brush‐border membranes from pig kidney

“…Distinction between the two subtypes of adenosine receptors is usually made on the basis of the rank orders of potency of agonists and antagonists. Recently, the existence of another adenosine receptor subtype (A3), not related to the adenylate cyclase system, has been described (Ribeiro & Sebastiao, 1985;1986;Sebastiao & Ribeiro, 1988). The A3 adenosine receptor subtype is related to calcium channels and has a different order of potency of agonists and antagonists from Al or A2 subtypes.…”