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REGULATION OF CATECHOLAMINE RELEASE FROM THE ADRENAL MEDULLA UNDER THE PHYSIOLOGICAL STRESS RESPONSE

Kuri, Barbara Alison

Abstract Details

2010, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
Release of catecholamine from the adrenal glands is a highly regulated process. The chromaffin cells of the adrenal medulla are the parenchymal cells of the adrenal gland and are capable of releasing catecholamine (adrenaline and noradrenaline) and neuroactive peptides into the circulation. Under autonomic nervous control, the innervating splanchnic nerve directs the release of catecholamine. In this study, we show how chronic intermittent hypoxia (CIH), a common form of metabolic stress, affects the release of catecholamine from the adrenal chromaffin cells, in situ. Using electrophysiological capacitance recording techniques we show that exposure to CIH results in an increase of the amount of catecholamine available for release, upon a given stimulus, through the recruitment of catecholamine containing granules to the readily releasable pool. We show that this is possible through the generation of reactive oxygen species (ROS) and subsequent activation of protein kinase C (PKC). To further address the regulation of catecholamine release under sympathetic stimulation we developed a bipolar stimulation protocol that mimics stimulation frequencies at rest and under burst mode stress firing. Using an in situ adrenal gland slice preparation we show that there is an activity dependent regulation of catecholamine release involving pituitary adenylate cyclase activating peptide (PACAP) which is released from the splanchnic nerve under conditions mimicking the burst mode stress firing. We show that PACAP acts through a novel mechanistic pathway that is independent of the conventional sympathetic cholinergic pathway. This characteristic of PACAP makes it an ideal neurotransmitter under high intensity, burst mode sympathetic firing, in that it does not desensitize like the cholinergic pathway. We show that PACAP acts through a G-protein coupled receptor to activate phospholipase C (PLC) which in turn activates PKC. Activation of PKC plays a role in increasing the activity of the sodium calcium exchanger (NCX) in the forward direction to depolarize the cell membrane to potentials that increase the open probability of a Ni2+ sensitive, low voltage activated Ca2+ channel. It is the influx of Ca2+ through this channel to generate the Ca2+ dependent release of catecholamine.
Corey Smith, PhD (Advisor)
Carole Liedtke, PhD (Committee Member)
Cathy Carlin, PhD (Committee Member)
Ted Dick, PhD (Committee Member)
Andrea Romani, PhD (Committee Chair)
Steve Jones, PhD (Committee Member)
149 p.

Recommended Citations

Citations

  • Kuri, B. A. (2010). REGULATION OF CATECHOLAMINE RELEASE FROM THE ADRENAL MEDULLA UNDER THE PHYSIOLOGICAL STRESS RESPONSE [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1257519626

    APA Style (7th edition)

  • Kuri, Barbara. REGULATION OF CATECHOLAMINE RELEASE FROM THE ADRENAL MEDULLA UNDER THE PHYSIOLOGICAL STRESS RESPONSE. 2010. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1257519626.

    MLA Style (8th edition)

  • Kuri, Barbara. "REGULATION OF CATECHOLAMINE RELEASE FROM THE ADRENAL MEDULLA UNDER THE PHYSIOLOGICAL STRESS RESPONSE." Doctoral dissertation, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1257519626

    Chicago Manual of Style (17th edition)