Exposure of an organism to a stressor results in a primary stress response. A part of this response involves the release of the catecholamines (CA), adrenaline (ADR) and noradrenaline (NADR), which exert their actions by binding to specific membrane binding sites or receptors termed adrenergic receptors or adrenoceptors (ARs). Continuous exposure to a hormone results in a decrease in the responsiveness of the cell. This process, termed desensitization may reduce the cell's responsiveness only to that hormone (homologous) or to another agonist (heterologous). Moreover, prolonged agonist exposure may result in the internalization (sequestration) and possible degradation of the receptor (down-regulation). These processes have been well studied for the three beta-AR subtypes in mammals, however little is known about how beta-ARs are regulated in teleost fish.
The goal of this thesis was to examine the regulation of the beta-ARs in two species of teleosts, the rainbow trout (Oncorhynchus mykiss ) and the black bullhead (Ameiurus melas). Fish were exposed to various stressors including prolonged agonist exposure, physical exertion and hypercarbia and receptor binding characteristics [affinity (K d) and number of binding sites (Bmax)] as well as function were examined. Chasing to exhaustion and prolonged feeding of the beta-agonist clenbuterol significantly reduced the Bmax of hepatic beta 2-ARs in rainbow trout by 27% and 33%, respectively. In contrast, exposure to hypercarbia did not significantly affect rainbow trout gill beta-ARs. Pharmacological characterization of the gill beta-AR supports an atypical classification compared with the three classic mammalian subtypes. No significant differences were observed in binding parameters for bullhead hepatic beta-ARs after a 24 hour exposure to the beta-agonist isoproterenol or a 1 hour air-exposure. However, air-exposure did result in a moderate desensitization in CA-stimulated hepatic glucose production. Phylogenetic analysis groups the bullhead hepatic beta-AR with the mammalian beta3-ARs, which is not supported by the pharmacological classification of a beta2-AR subtype. This study was the first to comparatively examine 3-AR regulation for different subtypes of teleost beta-ARs. Findings suggest beta-ARs in teleosts possess different sensitivities to down-regulation and desensitization as is seen with the different mammalian beta-AR subtypes.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/29101 |
| Date | January 2004 |
| Creators | Dugan, Stephen G |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 116 p. |
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