Atrial natriuretic peptide (ANP) causes mast cell degranulation in rats in vivo and in vitro but is bronchodilator in humans. The aim of this study was to investigate the wheal and flare dose-response to intradermal injection of a-human ANP in normal humans. Eight normal subjects received five 30 gl injections containing 1, 10, 39, 78, 117 pmol ANP and one each of normal saline, histamine 675 pmol and substance P 30 pmol. Maximum ANP flare response was greater but not significantly than that to saline at 1.55 ± 0.6 (mean ± s.e. mean) compared with 0.42 ± 0.17 cm2, but much less than to histamine 9.86 ± 0.97 or to substance P 12.5 ± 1.2. Maximum ANP wheal response was significantly greater than that to saline at 0.38 ± 0.08 compared with 0.18 ± 0.05 cm2 (difference between means 0.20, 95% CI 0.05, 0.35), but much less than to histamine 0.75 ± 0.06 or to substance P 1.05 ± 0.08 cm2. No dose-response to ANP was demonstrated, though responses to the highest dose differed significantly from those to the lowest dose studied. We conclude that human cutaneous responses to ANP differ from those of animals and that the skin is less responsive than other tissues in humans.

Lactose is commonly used as a carrier for inhaled drugs. Twenty healthy volunteers without respiratory symptoms inhaled seven different doses of lactose and a placebo (empty) dose through the four place Diskhaler® device, in order to determine the lowest dose that could be reliably sensed. The minimum dose for which all subjects reported taste or feel sensations was 10 mg. This has implications regarding the amount of carrier used in future drug delivery systems.

The aim of this study was to investigate whether the wheal and flare responses to intradermal injection of hypertonic (4.5%) saline (HTS) were inhibited by local injection of 1% lignocaine. Eight normal subjects were studied on one occasion. Lignocaine (0.125 ml) was infiltrated at four sites on one forearm and normal saline on the other. Five minutes later, duplicate intradermal injections of 30 gl of histamine (22.5 nmol ml-'), substance P (1 nmol ml-'), HTS and normal saline were given coded and in random order, one of each pair to each forearm. Lignocaine inhibited flare responses to histamine, substance P and HTS by 56% (P < 0.01), 78% (P < 0.01) and 77% (P < 0.05) respectively suggesting similar involvement of an axon reflex. Wheal to histamine was inhibited by 31% (P < 0.02) and to substance P by 33% (P < 0.05) but not to HTS. This suggests that the mechanism of wheal response to HTS differs from that of histamine and substance P.