Inhibition of mast cell adenosine responsiveness by chronic exposure to adenosine receptor agonists.
Mast cell adenosine receptors are up-regulated functionally and numerically by chronic exposure to receptor antagonists, but their response to long-term treatment with receptor agonists has not been studied. To address this issue cultured mouse bone marrow-derived mast cells were exposed to N-ethylcarboxamide adenosine (NECA), an adenosine receptor agonist that augments stimulated mast cell mediator release. Cells grown for 3 days in 1 nM NECA responded normally to A23187 or antigen in releasing beta-hexosaminidase, but the ability of exogenous adenosine to potentiate this mediator release was attenuated markedly. This inhibition of adenosine responsiveness was partially present after 10 min of 1 microM NECA exposure and complete after 4 hr. The inhibitory effects could be reversed by washing NECA-exposed cells and returning them to culture for more than 4 hr. The adenosine present in the fetal calf serum coupled with deoxycoformycin attenuated mast cell adenosine responsiveness. The NECA-treated cells also exhibited a hyporesponsiveness to adenosine's augmentation of cell cyclic AMP content. This hyporesponsiveness was specific for adenosine receptors in that exogenous isoproterenol was able to increase cyclic AMP levels to a similar degree in both control and NECA-treated cells. Thus, chronic NECA exposure induces a homologous desensitization of mast cell adenosine receptors.
Marquardt
D L
DL
Department of Medicine, University of California, San Diego School of Medicine, San Diego.
Walker
L L
LL
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000502:physiology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015649:Pentostatin; D011983:Receptors, Purinergic / Q000187:drug effects*; D013189:SRS-A / Q000378:metabolism; D013997:Time Factors; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D011983:Receptors, Purinergic; D013189:SRS-A; D003070:Coformycin; D019830:Adenosine-5'-(N-ethylcarboxamide); D000001:Calcimycin; D015649:Pentostatin; D000242:Cyclic AMP; D001619:beta-N-Acetylhexosaminidases; D000241:Adenosine; D007545:Isoproterenol