Kirkup A J, Eastwood C, Grundy D, Chessell I P, Humphrey P P
Department of Biomedical Science, University of Sheffield, Western Bank.
Br J Pharmacol. 1998 Nov;125(6):1352-60. doi: 10.1038/sj.bjp.0702202.
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. Adenosine (0.03-10 mg kg(-1), i.v.), NECA (0.3-300 microg kg(-1), i.v.) and the A1 receptor agonist, GR79236 (0.3-1000 microg 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 A2A receptor antagonist, ZM241385 (3 mg kg(-1), i.v.), antagonized the hypotensive effect of NECA but none of the effects of GR79236. The A2A receptor agonist, CGS21680 (0.3-300 microg kg(-1), i.v.), and the A3 receptor agonist, IB-MECA (0.3-300 microg 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. Bethanechol (300 microg 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. In summary, A1 and A2B and/or A2B-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.
我们研究了腺苷受体激动剂和拮抗剂对戊巴比妥钠麻醉大鼠供应空肠的肠系膜传入神经放电的影响。腺苷（0.03 - 10 mg kg⁻¹，静脉注射）、NECA（0.3 - 300 μg kg⁻¹，静脉注射）和A1受体激动剂GR79236（0.3 - 1000 μg kg⁻¹，静脉注射），每一种都能引起传入神经活动、空肠内压、低血压和心动过缓的剂量依赖性增加。A1受体拮抗剂DPCPX（3 mg kg⁻¹，静脉注射）能拮抗GR79236的所有作用，但仅能拮抗腺苷和NECA的血流动力学作用。A2A受体拮抗剂ZM241385（3 mg kg⁻¹，静脉注射）能拮抗NECA的降压作用，但不能拮抗GR79236的任何作用。A2A受体激动剂CGS21680（0.3 - 300 μg kg⁻¹，静脉注射）和A3受体激动剂IB - MECA（0.3 - 300 μg kg⁻¹，静脉注射），每一种都仅引起剂量依赖性低血压。随后静脉注射腺苷（3 mg kg⁻¹）引起传入神经活动、空肠内压增加和心动过缓。ZM241385（3 mg kg⁻¹，静脉注射）能拮抗CGS21680的降压作用，但不能拮抗腺苷的作用。氨甲酰甲胆碱（300 μg kg⁻¹，静脉注射）引起传入神经活动、空肠内压增加、低血压和心动过缓。然而，尽管腺苷（3 mg kg⁻¹，静脉注射）引起的空肠内压升高较小，但它引起的传入神经活动增加比氨甲酰甲胆碱更大。总之，A1和A2B和/或A2B样受体介导了腺苷诱导的麻醉大鼠肠系膜传入神经活动和空肠内压增加。此外，空肠内压升高并不能完全解释腺苷引起的肠系膜传入神经兴奋。
