Activation by ATP of a P2U 'nucleotide' receptor in an exocrine cell

Br J Pharmacol. 1995 May;115(2):321-9. doi: 10.1111/j.1476-5381.1995.tb15880.x.

Abstract

1. We employed the perforated patch whole-cell technique to investigate the effects of ATP and other related nucleotides on membrane conductances in avian exocrine salt gland cells. 2. ATP (10 microM-1 mM) evoked an increase in maxi-K+ and Cl- conductances with a reversal potential of -35 mV. At lower concentrations of ATP (< or = 100 microM) responses were generally oscillatory with a sustained response observed at higher concentrations (> or = 200 microM). 3. Both oscillatory and sustained responses were abolished by the removal of bath Ca2+. In cells preincubated in extracellular saline containing reduced Ca2+, the application of ATP resulted in a transient increase in current. 4. As increasing concentrations of ATP (and related nucleotides) evoked a graded sequence of events with little run-down we were able to establish a rank order of potency in single cells. The order of potency of ATP analogues and agonists of the various P2-receptor subtypes was UTP > ATP = 2-methylthio-ATP > ADP. Adenosine (1 microM-1 mM), AMP (1 microM-1 mM), alpha,beta-methylene-ATP (1 microM-1 mM) and beta,gamma-methylene-ATP (1 microM-1 mM) were without effect. 5. In conclusion, although unable to preclude a role for a P2Y-receptor, our results suggest that ATP binds to a P2U-receptor increasing [Ca2+]i and subsequently activating Ca(2+)-sensitive K+ and Cl- currents.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / pharmacology
  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Calcium / metabolism
  • Chlorides / metabolism
  • Ducks
  • Exocrine Glands / cytology
  • Exocrine Glands / drug effects*
  • Exocrine Glands / metabolism
  • Nasal Cavity / metabolism
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Receptors, Purinergic P2 / drug effects*
  • Receptors, Purinergic P2 / metabolism
  • Uridine Triphosphate / pharmacology

Substances

  • Chlorides
  • Receptors, Purinergic P2
  • 5'-adenylyl (beta,gamma-methylene)diphosphonate
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Adenosine
  • alpha,beta-methyleneadenosine 5'-triphosphate
  • Potassium
  • Calcium
  • Uridine Triphosphate