ATP and endogenous agonists inhibit evoked [3H]-noradrenaline release in rat iris via A1 and P2y-like purinoceptors

Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):352-7. doi: 10.1007/BF00171333.


Effects of ATP, adenosine and purinoceptor antagonists on field stimulation-evoked (3 Hz, 2 min) [3H]-noradrenaline overflow were investigated in the rat isolated iris. ATP and adenosine inhibited the evoked overflow of [3H]-noradrenaline. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) shifted the concentration-response curve of ATP to the right in a concentration-dependent manner, but with a potency (-log KB = 7.88) much lower than expected for an A1 adenosine receptor. In the continuous presence of DPCPX, the ATP-induced prejunctional inhibition was unaffected by suramin (100 mumol/l) and DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, 50 mumol/l) but was antagonized by the P2Y-receptor antagonist cibacron blue (= reactive blue 2; 30 and 100 mumol/l, -log KB = 4.7) and alpha,beta-methylene-ATP (10 mumol/l). Whereas the evoked [3H]-noradrenaline overflow was unaffected by suramin and DIDS, cibacron blue and alpha,beta-methylene-ATP caused a small and transient increase. Cibacron blue at 30 mumol/l failed to antagonize the inhibition of evoked [3H]-noradrenaline overflow that adenosine produced in the absence of DPCPX. Basal [3H]-noradrenaline overflow was enhanced by cibacron blue, not changed by alpha,beta-methylene-ATP and DIDS, and decreased by suramin. The results show that exogenous ATP inhibits sympathetic neurotransmission in the rat iris via A1 and P2Y-like purinoceptors. The latter have a low apparent affinity for cibacron blue and probably are blocked by alpha,beta-methylene-ATP. Under the present conditions, endogenous purines exert a tonic inhibition not only via A1- but also via these P2Y-receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Adenosine / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Electric Stimulation
  • In Vitro Techniques
  • Iris / metabolism*
  • Norepinephrine / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Purinergic P1 Receptor Antagonists
  • Purinergic P2 Receptor Antagonists
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P1 / drug effects*
  • Receptors, Purinergic P2 / drug effects*
  • Suramin / pharmacology
  • Synaptic Transmission / drug effects
  • Triazines / pharmacology
  • Xanthines / pharmacology


  • Protein Synthesis Inhibitors
  • Purinergic P1 Receptor Antagonists
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P1
  • Receptors, Purinergic P2
  • Triazines
  • Xanthines
  • Cibacron Blue F 3GA
  • Suramin
  • Adenosine Triphosphate
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Adenosine
  • alpha,beta-methyleneadenosine 5'-triphosphate
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • Norepinephrine