A1 adenosine receptors inhibit chloride transport in the shark rectal gland: Dissociation of inhibition and cyclic AMP

Grant G. Kelley, Eric M. Poeschla, Harold V. Barron, John N. Forrest

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

In the in vitro perfused rectal gland of the dogfish shark (Squalus acanthias), the adenosine analogue 2-chloroadenosine (2Clado) completely and reversibly inhibited forskolin-stimulated chloride secretion with an IC50 of 5 nM. Other A1 receptor agonists including cyclohexyladenosine (CHA), N-ethylcarboxamideadenosine (NECA) and R-phenylisopropyladenosine (R-PIA) also completely inhibited forskolin stimulated chloride secretion. The "S" stereoisomer of PIA (S-PIA) was a less potent inhibitor of forskolin stimulated chloride secretion, consistent with the affinity profile of PIA stereoisomers for an A1 receptor. The adenosine receptor antagonists 8-phenyltheophylline and 8-cyclopentyltheophylline completely blocked the effect of 2Clado to inhibit forskolin-stimulated chloride secretion. When chloride secretion and tissue cyclic (c)AMP content were determined simultaneously in perfused glands, 2Clado completely inhibited secretion but only inhibited forskolin stimulated cAMP accumulation by 34-40%, indicating that the mechanism of inhibition of secretion by 2Clado is at least partially cAMP independent. Consistent with these results, A1 receptor agonists only modestly inhibited (9-15%) forskolin stimulated adenylate cyclase activity and 2Clado markedly inhibited chloride secretion stimulated by a permeant cAMP analogue, 8-chlorophenylthio cAMP (8CPT cAMP). These findings provide the first evidence for a high affinity A1 adenosine receptor that inhibits hormone stimulated ion transport in a model epithelia. A major portion of this inhibition occurs by a mechanism that is independent of the cAMP messenger system.

Original languageEnglish (US)
Pages (from-to)1629-1636
Number of pages8
JournalJournal of Clinical Investigation
Volume85
Issue number5
DOIs
StatePublished - May 1990

    Fingerprint

Keywords

  • Adenosine
  • Adenosine receptors
  • Adenylate cyclase
  • Chloride transport
  • cAMP

ASJC Scopus subject areas

  • Medicine(all)

Cite this