EFFECT OF PUTATIVE PEPTIDE NEUROTRANSMITTERS ON CUTANEOUS VASCULAR-PERMEABILITY IN THE RAT

1. The effects on cutaneous vascular permeability of substance P. physalaemin, eledoisinrelated peptide, bradykinin, somatostatin, neurotensin, methionine enkephalin, vasoactive intestinal peptide, cholecystokinin and pentagastrin were investigated in rats using a quantitative Evans blue dye leakage technique to estimate plasma exudation. 2. Substance P, physalaemin, eledoisin-related peptide, bradykinin, somatostatin and neurotensin produced plasma exudation, neurotensin being the most potent of the peptides tested. The high potency of neurotensin would suggest that this peptide might play a role in local regulation of the microcirculation in some organs. 3. Pretreatment of rats with mepyramine and methysergide significantly reduced responses to substance P (5×10-9 mol) and neurotensin (5×10-9 mol). 4. Responses to neurotensin (5×10-11 and 5×10-10 mol) were almost abolished by mepyramine and methysergide and also be pretreatment of skin sites with compound 48/80. The response to substance P (5×10-10 mol) was not reduced by compound 48/80 but was reduced by mepyramine and methysergide. The response to substance P (5×10-9 mol) was reduced by both treatments but was not abolished. 5. No significant interactions were found between any of the peptide combinations tested. 6. The effect of neurotensin was significantly potentiated by 5-hydroxytryptamine, PGE1 and ATP. 7. It was concluded that substance P has both a direct action to increase vascular permeability in rat skin and an indirect action mediated by amine release from mast cells, whereas neurotensin has mainly an indirect amine-releasing action. © 1979 Springer-Verlag.