title: Endogenous adenosine is an autacoid feedback inhibitor of chloride transport in the shark rectal gland.
abstract: The present studies define the physiologic role of endogenous adenosine in the perfused shark rectal gland, a model epithelia for hormone-stimulated chloride transport. Chloride ion secretion, and venous adenosine and inosine concentrations increased in parallel in response to hormone stimulation. From a basal rate of 157 +/- 26 mu eq/h per g, chloride secretion increased to 836 +/- 96 and 2170 +/- 358 with 1 and 10 microM forskolin, venous adenosine increased from 5.0 +/- 1 to 126 +/- 29 and 896 +/- 181 nM, and inosine increased from 30 +/- 9 to 349 +/- 77 and 1719 +/- 454 nM (all P less than 0.01). Nitrobenzylthioinosine (NBTI), a nucleoside transport inhibitor, completely blocked the release of adenosine and inosine. Inhibition of chloride transport with bumetanide, an inhibitor of the Na+/K+/2Cl- cotransporter, or ouabain, an inhibitor of Na+/K+ ATPase activity, reduced venous adenosine and inosine to basal values. When the interaction of endogenous adenosine with extracellular receptors was prevented by adenosine deaminase, NBTI, or 8-phenyltheophylline, the chloride transport response to secretagogues increased by 1.7-2.3-fold. These studies demonstrate that endogenous adenosine is released in response to hormone-stimulated cellular work and acts at A1 adenosine receptors as a feedback inhibitor of chloride transport.
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: O S
authors.initials: OS
authors.lastname: Aassar
authors.forename: J N
authors.initials: JN
authors.lastname: Forrest
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004284:Dogfish; D005246:Feedback; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D012491:Salt Gland / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002712:Chlorides; D005576:Colforsin; D013868:Thioinosine; D007288:Inosine; D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine