Endogenous adenosine is an autacoid feedback inhibitor of chloride transport in the shark rectal gland.
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.
Kelley
G G
GG
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Aassar
O S
OS
Forrest
J N
JN
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
D002712:Chlorides; D005576:Colforsin; D013868:Thioinosine; D007288:Inosine; D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine