Immune-related intestinal chloride secretion. II. Effect of adenosine on T84 cell line.
The inflammatory mediator adenosine caused sustained Cl- secretion across monolayers of T84 cells. The effect was promptly reversed by the adenosine receptor antagonist 8-phenyltheophylline and appeared to be mediated through an adenosine A2-receptor [rank order of potency: 5'-(N-ethyl)-carboxamido-adenosine (NECA) greater than adenosine greater than (-)-N6-(phenylisopropyl)adenosine (PIA) greater than or equal to (+)-PIA]. High doses of adenosine and its analogues increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) but not guanosine 3',5'-cyclic monophosphate (cGMP) or free cytosolic Ca2+. However, lower concentrations of adenosine had maximal effects on Cl- secretion with little or no effect on cAMP. In other respects, Cl- secretion resembled that induced by cAMP-mediated secretagogues such as vasoactive intestinal peptide (VIP). Addition of both low and high doses of NECA activated basolateral K+ and apical Cl- channels, exhibited synergism with Ca2(+)-mediated secretagogues, did not produce additive effects with VIP or Escherichia coli heat-stable enterotoxin, and was associated with cAMP-dependent protein kinase-mediated protein phosphorylation. The results suggest that either adenosine mobilizes an intracellular pool of cAMP that is extremely efficiently coupled to the cAMP-dependent protein kinase and is thereafter rapidly destroyed or that second messenger(s) other than cAMP, cGMP, or Ca2+ are able to activate Cl- secretion in the T84 cell line. In the latter case, such messenger(s), as yet unidentified, might represent a final common pathway for cyclic nucleotide-activated Cl- secretion.
Barrett
K E
KE
Department of Medicine, University of California, San Diego 92103.
Cohn
J A
JA
Huott
P A
PA
Wasserman
S I
SI
Dharmsathaphorn
K
K
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D007700:Kinetics; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D002712:Chlorides; D004573:Electrolytes; D015762:2-Chloroadenosine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D006632:Histamine; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D011494:Protein Kinases; D006152:Cyclic GMP; D000241:Adenosine; D002118:Calcium