Secretion from chromaffin cells is controlled by chromogranin A-derived peptides.
Chromogranin A (CGA) is the major protein of the secretory granule from chromaffin cells and also is found in a variety of endocrine cells. Although the sequence of this acidic glycoprotein has been elucidated recently, its biological function is unknown. Here we have purified CGA from chromaffin granules; the final preparation contained the 74-kDa native CGA together with two degradation products--three bands near 60 kDa and a single band of 43 kDa. This preparation was found to inhibit (a maximum inhibition of 60% at 1 microM) the nicotine-induced, but not the high K+-evoked, catecholamine secretion from bovine chromaffin cells maintained in primary culture. Spontaneous release was also affected in the nanomolar CGA protein concentration range. The observation that the inhibitory effect is strictly dependent on a preincubation step together with the modification of the CGA protein profile during this preincubation step suggests that the degradation peptide(s) rather than the 74-kDa native CGA--the approximately equal to 60-kDa bands or the 43-kDa singlet band--is actually involved in secretory cell activity. This was demonstrated by using trypsin-generated peptides that were inhibitory without the preincubation period. The finding that unprocessed CGA is not active on chromaffin cell secretion suggests that this molecule is a precursor of a peptide(s) that is able to regulate catecholamine secretion. Thus, the present data suggest that a CGA-derived peptide(s) could exert a feedback control on chromaffin cell secretory activity--a mechanism that might be of importance during stress situations.
Institut National de la Santé et de la Recherche Médicale Unité 44, Centre de Neurochimie du Centre National de la Recherche Scientifique, Strasbourg, France.
J P
JP
Simon
M F
MF
Bader
D
D
Aunis
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002837:Chromaffin Granules / Q000502:physiology; D053379:Chromogranin A; D002864:Chromogranins / Q000502:physiology*; D005246:Feedback; D066298:In Vitro Techniques; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology; D014357:Trypsin / Q000378:metabolism
D053379:Chromogranin A; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D014357:Trypsin