Characterization and tissue location of the neural adenosine receptor in the rat ileum

The aim of the present investigation was to characterize and determine the tissue location of the adenosine receptors present in the rat ileum using a method that detects drug action on the cholinergic nerves innervating the longitudinal and circular muscles. The non‐selective adenosine agonist, NECA (10 and 100 nM) caused significant concentration‐related reductions in the circular muscle responses to transmural stimulation over the frequency range of 2.5–40 Hz, but did not affect the responses of the longitudinal muscle, nor did it reduce the muscle responses of the guinea‐pig ileum. The affinity order of antagonists at inhibiting the effect of NECA on the circular muscle was: CPDPX>8‐PT>DMPX with apparent pA2 values of 9.31, 7.54 and 5.63 respectively. CPDPX (10–100 nM) caused parallel displacements of the concentration‐effect curves to CPA with a pKb value of 9.15 and Schild slope of 1.03. The agonists previously tested in the rat jejunum peristaltic reflex preparation were also shown to inhibit responses of the rat ileum in the following decreasing order of potency: CPA>NECA>2‐CADO>R‐PIA>S‐PIA>>PAA. In addition, CHA and CCPA were also potent agonists. NECA (100 nM) and CPA (32 nM) did not inhibit carbachol (1 μM)‐induced tone of tissues pre‐treated with TTX (1 μM). In conclusion, the rat ileum contains inhibitory A1 adenosine receptors situated on cholinergic nerve endings innervating the circular muscle. British Journal of Pharmacology (1999) 126, 1269–1275; doi:10.1038/sj.bjp.0702411