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

• Published in: The Journal of clinical investigation 1990-05, Vol.85 (5), p.1629-1636
• Main Authors: KELLEY, G. G, POESCHLA, E. M, BARRON, H. V, FORREST, J. N
• Format: Article
• Language: English
• Subjects: 2-Chloroadenosine - pharmacology; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Chlorides - metabolism; Colforsin - pharmacology; Cyclic AMP - metabolism; Dogfish; Female; In Vitro Techniques; Kinetics; Male; Medical sciences; Metabolic diseases; Perfusion; Receptors, Purinergic - drug effects; Receptors, Purinergic - physiology; Salt Gland - drug effects; Salt Gland - metabolism; Somatostatin - pharmacology; Theophylline - analogs & derivatives; Theophylline - pharmacology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI114614

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-phenylisopropyl-adenosine (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.