title: A1 adenosine receptors inhibit chloride transport in the shark rectal gland. Dissociation of inhibition and cyclic AMP.
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-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.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: G G
authors.initials: GG
authors.lastname: Kelley
authors.forename: E M
authors.initials: EM
authors.lastname: Poeschla
authors.forename: H V
authors.initials: HV
authors.lastname: Barron
authors.forename: J N
authors.initials: JN
authors.lastname: Forrest
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004284:Dogfish; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010477:Perfusion; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D012491:Salt Gland / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002712:Chlorides; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D005576:Colforsin; D013004:Somatostatin; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000262:Adenylyl Cyclases; D000241:Adenosine