Characterization of adenosine receptors evoking excitation of mesenteric afferents in the rat

Abstract

1. We examined the effects of adenosine receptor agonists and antagonists on the discharge of mesenteric afferent nerves supplying the jejunum in pentobarbitone sodium-anaesthetized rats.

2. Adenosine (0.03–10 mg kg⁻¹, i.v.), NECA (0.3–300 μg kg⁻¹, i.v.) and the A₁ receptor agonist, GR79236 (0.3–1000 μg kg⁻¹, i.v.), each induced dose-dependent increases in afferent nerve activity and intrajejunal pressure, hypotension and bradycardia. The A₁ receptor antagonist, DPCPX (3 mg kg⁻¹, i.v.), antagonized all the effects of GR79236 but only the haemodynamic effects of adenosine and NECA. The A_2A receptor antagonist, ZM241385 (3 mg kg⁻¹, i.v.), antagonized the hypotensive effect of NECA but none of the effects of GR79236.

3. The A_2A receptor agonist, CGS21680 (0.3–300 μg kg⁻¹, i.v.), and the A₃ receptor agonist, IB-MECA (0.3–300 μg kg⁻¹, i.v.), each induced only a dose-dependent hypotension. Subsequent administration of adenosine (3 mg kg⁻¹, i.v.) induced increases in afferent nerve activity and intrajejunal pressure and bradycardia. ZM241385 (3 mg kg⁻¹, i.v.) antagonized the hypotensive effect of CGS21680 but not the effects of adenosine.

4. Bethanechol (300 μg kg⁻¹, i.v.) evoked increases in afferent nerve activity and intrajejunal pressure, hypotension and bradycardia. However, adenosine (3 mg kg⁻¹, i.v.) evoked greater increases in afferent nerve activity than bethanechol despite inducing smaller increases in intrajejunal pressure.

5. In summary, A₁ and A_2B and/or A_2B-like receptors evoke adenosine-induced increases in mesenteric afferent nerve activity and intrajejunal pressure in the anaesthetized rat. Furthermore, elevations in intrajejunal pressure do not wholly account for adenosine-evoked excitation of mesenteric afferent nerves.

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