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

Br J Pharmacol. 1998 Nov;125(6):1352-60. doi: 10.1038/sj.bjp.0702202.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology*
  • Adenosine-5'-(N-ethylcarboxamide) / pharmacology
  • Analgesics / pharmacology*
  • Animals
  • Bethanechol / pharmacology
  • Female
  • Jejunum / innervation*
  • Male
  • Muscarinic Agonists / pharmacology
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology
  • Neurons, Afferent / ultrastructure*
  • Phenethylamines / pharmacology
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P1 / physiology*

Substances

  • Analgesics
  • Muscarinic Agonists
  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Bethanechol
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
  • Adenosine-5'-(N-ethylcarboxamide)
  • Adenosine
  • N-((1S,trans)-2-hydroxycyclopentyl)adenosine