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Updated: Oct 13, 2026

Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents
Published on: May 16, 2022
Substance P, calcitonin gene-related peptide, and capsaicin release serotonin from cerebrovascular mast cells
A M Reynier-Rebuffel1, P Mathiau, J Callebert
1Laboratoire de Recherches Cérébrovasculaires, Unité Associée 641 Centre National de la Recherche Scientifique, Université Paris VII, France.
Abstract:
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 be stimulated by substance P (SP) and calcitonin gene-related peptide (CGRP), which are stored and released by sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that 5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a dose-dependent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve terminals by capsaicin. The simultaneous administration of CGRP and SP induced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We conclude that, as in classical connective tissue mast cells, the amine content of these granular cells can be released by a degranulation process induced by neuropeptides. The effects of capsaicin suggest that this phenomenon can be triggered by axon reflex of C fibers. The data also provide the first evidence of a synergistic action of SP and CGRP on mast cell degranulation.
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