Dual action of high energy adenine nucleotides in comparison with responses evoked by other adenine derivatives and intramural nerve stimulation on smooth muscle

Abstract

Fundic strips from stomach smooth muscle of the guinea-pig responded with a contraction preceded by a relatively small relaxation upon addition of the high energy adenine nucleotides ADP and ATP at 37°C. The contractile response was concentration-dependent in the range of 10 −8-10 −4 M, while the relaxation appeared at higher concentrations (10 −6-10 −4 M). The contractile phase observed in the presence of ADP or ATP was inhibited by the prostaglandin antagonist p-benzyl-4-(1-oxo-2-(4-chlorobenzyl)-3-phenylpropyl)phenyl phosphanate (N-0164; 5 × 10 −8 M). The low energy nucleotide AMP, adenosine and the ATP analogue β, γ-methyleneadenosine 5′-triphosphate caused relaxation of the stomach muscle. This relaxation was not affected by N-0164 (5 × 10 −8 M). Stimulation of the non-adrenergic inhibitory nerves caused relaxation of the muscle cells, in contrast to the effect of ATP. This seems to be in conflict with the purinergic nerve hypothesis. However, the relaxation evoked by field stimulation may have been due to adenosine if it can be assumed that ATP is degraded after its possible release from nerve terminals. Furthermore, the limited availability of ATP if released from nerves for the short period of stimulation is presumably ineffective to stimulate prostaglandin biosynthesis. The results suggest that synthesis of prostaglandins is promoted by the high energy adenine nucleotides ADP and ATP which induce contraction of stomach smooth muscle in contrast with the low energy adenine derivatives and stimulation of the intramural non-adrenergic nerves which produce muscle relaxation.