In view of calmodulin's widespread role in calcium-regulated processes, together with the requirement of Ca('2+) for chromaffin cell secretion, a possible role for calmodulin in translating the Ca('2+) signal for secretion is suggested. / Isolated bovine adrenal medullary cells were maintained in monolayer culture and their morphological and functional characteristics examined. The cultured chromaffin cell was found capable of accumulating exogenous amines via a high affinity uptake(,1)-like process which closely simulated the neuronal process in many respects but demonstrated neither stereo- nor structural selectivity. The accumulated amines appeared to be uniformly distributed within the chromaffin cell as they were released in parallel with and in equal proportion to the endogenous chromaffin cell catecholamines. This finding proved invaluable in designing a rapid reproducible method for assaying for catecholamine release from the chromaffin cells in culture. / Catecholamine secretion from the chromaffin cells in response to stimulation with either acetylcholine or a depolarizing concentration of K('+) is a Ca('2+)-dependent event. The stimulation-induced amine release was reduced in the presence of trifluoperazine, an antipsychotic agent and potent calmodulin antagonist. However, trifluoperazine blocked catecholamine release from the cultured chromaffin cells at a step distal from Ca('2+) entry, thus providing indirect evidence for a role for calmodulin in the secretory process. More direct evidence for a role for calmodulin in the process of secretion was provided with the use of antibodies raised against calmodulin. In this regard, erythrocyte ghost-mediated microinjection of calmodulin antibodies into viable cell cultures inhibited stimulus-evoked catecholamine secretion from the cultured cells without affecting amine accumulation into these cells. These findings support the hypothesis that calmodulin is important in translating the calcium signal for chromaffin cell secretion. On the other hand, calmodulin appears not to be involved in the catecholamine uptake process in these cells.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.72051 |
| Date | January 1985 |
| Creators | Kenigsberg, Rhoda Leah. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000222391, proquestno: AAINL24051, Theses scanned by UMI/ProQuest. |
Page generated in 0.002 seconds