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PubMed1976

Tachyphylaxis to topically applied steroids.

Acute tolerance to the vasoconstrictive effect of topically applied glucocorticoids in humans has recently been described. Similar acute tolerance to the antiproliferative properties of topically applied steroids in proliferating and normal hairless mouse epidermis is now shown to occur. Thus, at first, topically applied steroids cause profound inhibition of DNA synthesis and mitosis in the epidermis, but with continued treatment, DNA synthesis and mitosis recover and the tissue becomes insensitive to further stimulation. This suggests that there is an optimum approach to therapy with topically applied steroids that might reduce the incidence of side effects and improve therapeutic efficacy.

Administration, Topical↗
PubMed1983

The effect of prostaglandin E2 on histamine-stimulated calcium mobilization as a possible explanation for histamine tachyphylaxis in canine tracheal smooth muscle.

Isolated strips of canine tracheal smooth muscle rapidly lost their responsiveness to histamine when placed in a zero calcium Krebs buffer. Responsiveness to acetylcholine, however, was not rapidly lost, and following 120 min of incubation in zero calcium buffer with frequent washes, 10% of the contractile response still remained. The kinetics of each loss of response suggest that primarily a loosely bound source of calcium is mobilized by histamine and a more tightly bound source is mobilized by acetylcholine. Consistent with these data were the effects of the calcium antagonist verapamil. In normal calcium Krebs solution, dose-response curves to histamine were markedly reduced by verapamil while acetylcholine responses were relatively unaffected. In calcium depleted tracheal strips, indomethacin potentiated the calcium dose-response curve, determined by incremental readdition of calcium in the presence of histamine (10(-4) M), with comparatively little effect on the calcium dose-response curve in the presence of acetylcholine (10(-6) M). Also, in indomethacin pretreated tracheal strips, a reduction in the histamine-calcium dose-response curve could be produced by exogenous addition of 2.8 X 10(-9) M and 2.8 X 10(-8) M PGE2. In the acetylcholine-calcium responses there was a significant reduction only at 2.8 X 10(-8) M PGE2. These data suggest that histamine mobilizes primarily a loosely bound, possibly extracellular source of calcium necessary for contraction, and this histamine-stimulated calcium mobilization is sensitive to the effects of PGE2.

Acetylcholine↗
PubMed1977

Results of reflex photometric determinations of vasoconstriction after topical steroid application. Tachyphylaxis, relative and absolute refractory phase after single and multiple application of steroid.

After a repeated intensive topical application (4-h rhythm), there it is phase already after 28 h in which the cutaneous vessels are insensitive (refractory) to constrictor stimuli due to steroids. This refractory phase lasts for at least 68 h. A single local application of steroid likewise leads to a diminished vasoreactivity for a limited time. The relative refractory phase is limited to 96 h under the given experimental conditions.

Administration, Topical↗