Release of the predicted calcitonin gene-related peptide from cultured rat trigeminal ganglion cells

Abstract

Calcitonin gene-related peptide (CGRP) is a putative novel neuropeptide predicted on the basis of alternative RNA processing events of primary transcripts of the calcitonin gene. Distinct mRNAs encoding either calcitonin or CGRP are generated from the calcitonin gene RNA transcript in what appears to be a tissue-specific manner. The predicted peptide has now been detected immunocytochemically in discrete regions of the central and peripheral nervous systems and potent in vivo actions have been reported for centrally and peripherally administered synthetic CGRP. However, so far there is no evidence that CGRP is secreted or released by intact cells. The present experiments investigated the possible secretion of CGRP in vitro using primary dispersed cell cultures of the adult rat trigeminal ganglion, which previously has been found to contain large amounts of CGRP mRNA (ref. 2). We report here that immunoreactive CGRP is spontaneously released by cultured trigeminal ganglion cells and that secretion is stimulated by incubation in high potassium medium in a calcium-dependent fashion. Chromatographic characterization of the secreted CGRP-like immunoreactivity (CGRP-LI) isolated only one molecular form which appears to be similar or identical to the predicted rat CGRP (1-37).

Immunoelectron Microscopic Observation of Calcitonin Gene-Related Peptide(CGRP)-positive Nerves in the Dental Pulp of Rat Molars.

“…Physiological experiments have shown that antidromic stimulation of nerve fibers derived from the trigeminal sensory ganglion induces an increase in the content of pulpal substance P (OLGART et al, 1977), which is colocalized in the CGRP-containing nerve fibers (WAKISAKA et al, 1987), and also increases pulpal blood flow (GAZELIUS and OLGART, 1980). Furthermore, stimulation of trigeminal sensory neurons has demonstrated the antidromic release of CGRP in vitro (MASON et al, 1984). It is thus reasonable that CGRP is in possible collaboration with substance P released from nerves to act as vasodilator.…”

“…This characteristic of CGRP-immunoreactive nerve terminals suggests diverse functions for the mitochondria-rich nerve endings. Trigeminal sensory nerves possess the potential for antidromic release of CGRP (MASON, 1984), and CGRP manifests multiple functions such as trophic effects on vascular smooth muscle cells, fibroblasts and lymphocytes, as well as vascular effects (for review, HOLZER, 1988). Thus, the CGRPpositive nerve terminals associated with odontoblast may also be involved in some active-such as trophic -functions in addition to the receptive function .…”

Calcitonin gene‐related peptide is localised to human airway nerves and potently constricts human airway smooth muscle

“…CGRP is released by rat trigeminal ganglion cells in vitro (Mason et al, 1984) and it seems likely that CGRP may act as a neurotransmitter or neuromodulator. The distribution of CGRP in the spinal cord is similar to that of SP and suggests a sensory role for this peptide (Gibson et al, 1984).…”

Electrophysiological and mechanical effects of calcitonin gene‐related peptide on guinea‐pig atria

“…CGRP-immunoreactivity is found in heart particularly around the sinoatrial and atrioventricular node, as well as in periadventitial nerves in association with blood vessels (Manson et al, 1984;Wisenfeld-Hallin et al, 1984;Mulderry et al, 1985;Gennari & Fischer, 1985).…”