Stimulus response coupling in the carotid body: a role for metabolic signalling

[摘要] The mammalian carotid body (CB) is the primary sensory organ that responds to a reduction in arterial O\(_2\) tension. Activation of the CB and stimulation of its chemoafferent fibres evokes a series of well characterised cardiovascular and respiratory reflexes that act to restore normal O\(_2\) levels throughout the organism. A role for an elevated CB chemoafferent outflow in the aetiology and progression of a number of cardiorespiratory disease states has been identified, underlying the importance of understanding the signalling mechanisms required to activate the CB in hypoxia. In this thesis evidence is provided indicating that the CB response to hypoxia is a consequence of a reduction in mitochondrial energy metabolism and stimulation of the liver kinase B 1/AMP activated protein kinase signalling cascade. Questions also remain over the potential for other stimuli to acutely stimulate the CB. Observations described in this investigation suggest that the CB is not directly sensitive to glucose deprivation and that it preserves energy status in these conditions by metabolism of stored glycogen. Finally, chemoafferent outflow is, ultimately, dependent upon neurotransmission and small molecule neuromodulation. This thesis demonstrates a previously uncharacterised key functional role for adenosine derived from extracellular catabolism of ATP in mediating chemoafferent activity.

[发布机构] University:University of Birmingham;Department:School of Clinical and Experimental Medicine

[关键词] R Medicine;R Medicine (General)