Tachykinins and calcitonin gene-related peptide in relation to peripheral functions of capsaicin-sensitive sensory neurons

Abstract

Antidromic stimulation of sensory nerves or administration of capsaicin and SP in the guinea-pig induced vascular protein leakage with a similar pattern of distribution in different peripheral organs, characterized by a wide-spread but highly selective occurrence. The protein-extravasation responses in the tissues, following nerve stimulation or i.v. capsaicin, were highly correlated with the concentration of SP-LI. Systemic capsaicin treatment caused an almost total loss of SP-LI in visceral organs, in which the extravasation responses to capsaicin or nerve stimulation were also abolished. The ureter of the guinea-pig was most densely innervated by capsaicin-sensitive sensory nerves, which arrive at the rostral part of the ureter via the inferior mesenteric ganglion. The caudal ureter was mainly innervated from the pelvic nerves. The vascular permeability increase induced by SP or capsaicin was more pronounced in the ureter than in any other organ investigated. SP-LI, TK-LI and CGRP-LI coexist in sensory neurons of the guinea-pig and man, as shown by immunohistochemistry. These three kinds of immunoreactivity were found in sensory cell bodies with similar regional and terminal distribution patterns in both the central and peripheral areas. Systemic capsaicin treatment induced marked reduction of SP- and TK-LI in peripheral organs except for the ileum. CGRP-LI in the ureter was also sensitive to the capsaicin treatment. Characterization of the TK-LI (K12) of the guinea-pig ureter and lung, using ion-exchange chromatography and HPLC, demonstrated that at least three immunoreactive components corresponding to NKA, NPK and ELE were present. The major form of SP-LI eluted in the same position as synthetic SP. The NKA- and ELE-like components were also identified by HPLC in water extracts of human ureter. NKB was not detectable in the sensory neurons of the guinea-pig. Capsaicin caused an acute release of SP-, NKA- and ELE-like components from superfused slices of both the spinal cord and ureter of the guinea-pig in vitro. The release of tachykinins by capsaicin was calcium-dependent but tetrodotoxin-resistant. No detectable release of NKB- or NPK-LI was induced by capsaicin. Tachykinins share a common spectrum of biological activities with regard to hypotension, bronchoconstriction and protein extravasation when given systemically to guinea-pigs. The potency of the hypotensive action of tachykinins was similar. NKA and NPK evoked much stronger bronchoconstrictor effects than SP, while SP was more active than NKA in inducing vascular permeability changes.(ABSTRACT TRUNCATED AT 400 WORDS)