Prior exposure of macrophages to a low temperature enhances their cyclic AMP responses due to microtubule disruption.
Prior exposure of intact macrophages to a low temperature (4 degrees C) resulted in tremendous increases in their cAMP-generating responses to prostaglandin (PG) E1, epinephrine, adenosine, forskolin, and cholera toxin. The extent of the enhancement was dependent on the site of stimulation by these agents. The effect of cold exposure was (a) completely reversed by reexposure of the cold-treated cells to 37 degrees C; (b) mimicked by antimicrotubule agents, colchicine and vinblastine; (c) not further increased by colchicine or vinblastine treatment; and (d) efficiently antagonized by D2O and taxol, microtubule stabilizers. These results demonstrated that enhancement of cAMP generation by cold exposure was mediated through microtubule disruption. The effects of cold exposure and microtubule-disrupting agents on hormone-induced refractoriness was also studied. Macrophages stimulated at 37 degrees C by PGE1 became refractory to the subsequent stimulation by PGE1, regardless of whether the cells had been, or were subsequently, exposed to 4 or 37 degrees C. In contrast, cells stimulated by PGE1 in the presence of colchicine, or cells pretreated with PGE1 at 4 degrees C, responded to PGE1 rechallenge normally. The results suggested that disassembly of microtubules provides a condition unfavorable for development of receptor refractoriness, but never favors recovery therefrom.
Hazeki
K
K
Mori
Y
Y
Ui
M
M
D000470:Alkaloids / Q000494:pharmacology; D000527:Alprostadil; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D003080:Cold Temperature; D000242:Cyclic AMP / Q000378:metabolism*; D003903:Deuterium; D017666:Deuterium Oxide; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D017239:Paclitaxel; D011458:Prostaglandins E / Q000494:pharmacology; D014867:Water
D000470:Alkaloids; D011458:Prostaglandins E; D014867:Water; D003903:Deuterium; D000242:Cyclic AMP; D000527:Alprostadil; D017666:Deuterium Oxide; D017239:Paclitaxel; D003078:Colchicine