HUMAN AND RAT CUTANEOUS MAST-CELLS - INVOLVEMENT OF A G-PROTEIN IN THE RESPONSE TO PEPTIDERGIC STIMULI

Recent evidence suggests that peptides induce the release of mediators from rat peritoneal mast cell by means of a receptor-independent mech anism, possibly involving an interaction with sialic acid residues at the cell surface followed by the activation of a guanine nucleotide bi nding protein (G protein). We have now examined the potential involvem ent of sialic acid residues and of G protein stimulation in the activa tion of both human and rat cutaneous mast cells by neuropeptide Y, its C-terminal fragments and the wasp venom peptide, mastoparan. Neuropep tide Y-(18-36) was the most effective histamine releaser of the fragme nts tested, the order of potency being neuropeptide Y-(18-36)>neuropep tide Y-(22-36)>neuropeptide Y-(1-36). This order of potency suggests t hat the effects of the peptides are not mediated through classical NPY receptors. The hydrolysis of sialic acid residues by neuraminidase an d the inhibition of G proteins by benzalkonium chloride or pertussis t oxin significantly inhibited the secretory response of cutaneous mast cells to neuropeptide Y-(18-36) and mastoparan. These results demonstr ate that the peptidergic pathway described for the activation of perit oneal rat mast cells is also involved in the response of cutaneous hum an and rat mast cells to peptides.