Methacholine induces wheal‐and‐flare reactions in human skin but does not release histamine in vivo as assessed by the skin microdialysis technique

Abstract

A number of investigations have indicated that cholinergic agonists release histamine from isolated mast cells and suggested that cholinergic stimulation releases histamine in vivo. The purpose of this study was to investigate whether the cutaneous wheal-and-flare reaction induced by methacholine challenge in human skin involves histamine release as measured by the skin microdialysis technique. Five hollow dialysis fibers were inserted intradermally in forearm skin in eight healthy subjects. Each fiber was perfused with Kreb's-Ringer bicarbonate at a rate of 3 microliters/min. Dialysates were collected in 2-min fractions before skin challenge and for 20 min after intradermal injection of methacholine 10(-3)-10(-1) M, the vehicle, and a positive control, codeine phosphate 0.3 mg/ml. Histamine was assayed spectrofluorometrically. Methacholine caused a statistically significant dose-related wheal-and-flare reaction, the flare reaction to methacholine 10(-1) M being comparable with that seen with codeine 0.3 mg/ml. No significant histamine release was observed with methacholine, cumulative histamine release of 16 +/- 8 nM by methacholine 10(-1) M being similar to vehicle responses of 15 +/- 9 nM. Histamine release by codeine was 2524 +/- 435 nM. In conclusion, methacholine-induced wheal-and-flare reactions in human skin appeared not to involve histamine release from skin mast cells.

Administration of acetylcholine and vasoactive intestinal polypeptide to atopic eczema patients

“…In contrast, in vivo studies suggested that i.c. injections with methacholine, an analogue to ACh, does not induce the release of histamine from cutaneous mast cells (11). Indeed, in AE patients final flare size and pain sensation remained unchanged following ACh-application after cetirizine pretreatment, but pruritus was reported to be elevated.…”

“…In a recent study using the microdialysis technique it was reported that i.c. injections of methacholine did not induce the release of histamine from cutaneous mast cells (11). Therefore, we were interested to prove that cholinergic mediators cause pruritus in AE patients independently of histamine effects.…”

H1‐antihistamines: inverse agonism, anti‐inflammatory actions and cardiac effects

“…The ability of H 1 ‐antihistamines to inhibit weal and flare responses to inflammatory mediators which induce small or negligible amounts of histamine is not unique to bradykinin, having been reported also for methacholine [40,65] and platelet activating factor (PAF) [66,67]. The mechanism(s) by which H 1 ‐antihistamines abrogate these responses is far from clear.…”

Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema

“…Parallel action potentials spread antidromically via axon collaterals leading to stimulation of nerve fibers with concomitant release of neuropeptides such as substance P or calcitonin gene related peptide. The flare reaction is visible on the skin surface and can be evaluated as the efferent part of the axon reflex (36–39).…”