Studies on pruritogenic and histamine-releasing effects of some putative peptide neurotransmitters

Abstract

Pruritus, whealing and axon-reflex erythema appeared in human skin after intradermal injection of (i) several peptides with a putative transmitter function, i.e. vasoactive intestinal polypeptide (VIP) (10-7-10-4 M), [Gln4]-neurotensin (10-7-10-4 M), neurotensin (10-5-10-4 M) and secretin (10-5-10-4 M), which were compared with substance P (10:-7-10-5 M) previously shown to be one of the most potent histamine liberators when administered intradermally in humans; (ii) the basic polypeptide protamine (10-7-10-4 M); and (iii) histamine (0.3-10 μg/ml) and the histamine liberator compound 48/80 (0.3-10 μg/ml). The reactions were inhibited in a dose-related manner by the antihistamine mepyramine, indicating that the peptide-induced responses were mediated by released histamine. This was further confirmed by the histamine release observed when the peptides were incubated with rat peritoneal mast cells. In human skin, VIP was more potent than the other neuropeptides and had roughly the same potency as substance P. The two adjacent basic amino-acid residues and the amide substitution of the terminal C-group of VIP, in addition to its strong net basic charge, may explain its potency as a histamine releaser.