Nerve-mediated inhibition of mechanical activity in rabbit duodenum and the effects of desensitization to adenosine and several of its derivatives.

1. Inhibition of mechanical activity in longitudinal muscle strips of rabbit duodenum was induced by perivascular and intramural nerve stimulation.2. The effects of perivascular stimulation were abolished by phentolamine + propranolol, guanethidine, reserpine and by tetrodotoxin. The effects of intramural stimulation were abolished only by tetrodotoxin.3. Noradrenaline, phenylephrine, isoprenaline, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine each produced an inhibition of mechanical activity. The relative potencies of these agonists were noradrenaline>isoprenaline>phenylephrine>ATP>ADP>adenosine>AMP.4. Exposure of tissues to high concentrations of either ATP or adenosine desensitized the tissue to further exposure to ATP, ADP, AMP and adenosine, whilst the inhibitory effects of noradrenaline, phenylephrine and isoprenaline and of perivascular and intramural stimulation were unaffected. The effects of desensitization were reversible.5. It was concluded that the effects of intramural stimulation were mediated neither by noradrenaline nor by adenosine or its derivatives.