SUBSTANCE-P, CALCITONIN-GENE-RELATED PEPTIDE, AND CAPSAICIN RELEASE SEROTONIN FROM CEREBROVASCULAR MAST-CELLS

Rabbit leptomeningeal arteries contain granular cells resembling mast cells that frequently contact autonomic and sensory nerve profiles. In the present in vitro study, we determined whether these cells could b e stimulated by substance P (SP) and calcitonin gene-related peptide ( CGRP), which are stored and released by sensory C fibers. Immunohistoc hemistry of the middle cerebral artery showed that 5-HT was stored onl y in mast cell-like granules. This pool of 5-HT decreased in a dose-de pendent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve te rminals by capsaicin. The simultaneous administration of CGRP and SP i nduced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We co nclude that, as in classical connective tissue mast cells, the amine c ontent of these granular cells can be released by a degranulation proc ess induced by neuropeptides. The effects of capsaicin suggest that th is phenomenon can be triggered by axon reflex of C fibers. The data al so provide the first evidence of a synergistic action of SP and CGRP o n mast cell degranulation.