Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.643284
Title: Characterisation of acetylcholine and angiotensin II receptor mechanisms for cortisol secretion in bovine adrenocortical zona fasciculata/reticularis cells
Author: Clyne, Colin D.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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Abstract:
Numerous hormones and neurotransmitters have been reported to modulate steroid from the adrenal cortex. In particular, acetylcholine (ACh) and angiotensin II (AII) stimulate both aldosterone and cortisol secretion from the adrenocortical zona glomerulosa (zg) and zona fasciculata/reticularis (zfr) respectively. This study has investigated the cellular mechanisms by which ACh and AII stimulated cortisol secretion from bovine adrenal zfr cells maintained in primary culture. The ability of ACh and AII to stimulate cortisol secretion from zfr cells was assessed over experimental days 1 (initial isolation of cells) to 5. Freshly isolated cells secreted cortisol in response to ACh and AII. This steroidogenic response was significantly reduced or absent on day 2, and recovered over days 3 and 4, at which time cells were maximally responsive to these agents. The reduced secretory response on day 2 was accompanied by a paradoxical increase in phospholipase C( PLC) activation, indicating that stimulation of PLC by ACh and AII becomes uncoupled from stimulation of steroidogenesis at this time. In contrast, steroidogenic and second messenger responsiveness to adrenocorticotropin (ACTH) and adrenaline, which activate adenylate cyclase, increased over experimental days 1 to 4. This loss of steroidogenic responsiveness to ACh and AII was shown to occur through a defect in the protein kinase C-mediated stimulation of the steroidogenic pathway. The receptor subtype(s) mediating the steroidogenic responses to ACh and AII were characterised using selective antagonists. Hexahydro-sila-difenidol and p-fluoro-hexahydro-sila-difenidol were potent competitive antagonists of ACh-stimulated cortisol secretion with pA2 values of 8.68 and 7.96 respectively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.643284  DOI: Not available
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