Thromboxane-mediated neural reflexes in the heart and lung.
Our research centers on the investigation of neural control mechanisms that regulate heart and blood vessel function. We are particularly interested in identifying endogenous chemicals that stimulate sensory nerves from organs such as the heart or lung. Following identification of these chemicals, we seek to understand the cellular mechanism that allows these chemicals to stimulate sensory nerve endings. Understanding the mechanism of nerve stimulation will allow us to manipulate these events during abnormal or pathological conditions.
Stimulation of chemosensitive nerves from the heart: Using intact animal models such as the anesthetized rabbit, we are investigating whether endogenous chemicals such as thromboxanes and prostaglandins stimulate or modulate sensory nerve activity from the heart. We have recently reported that cardiac injections of thromboxanes stimulate sensory nerves in the heart that travel in the vagus nerve. Our next objective is to determine if the release of thromboxanes during myocardial ischemia (i.e. reduced blood flow to the heart as during a heart attack) stimulates sensory nerves leading to changes in heart and blood vessel function.
Gene expression in chemosensitive sensory neurons: Using molecular techniques, we are investigating the mechanism by which thromboxanes or other endogenous chemicals stimulate sensory nerves. Our first approach has been to investigate whether thromboxanes could stimulate sensory cells directly by interacting with receptors on the surface of nerve terminals within the heart. Sensory neurons are cultured and mRNA for the thromboxane receptor measured within individual cells to determine whether these cells transcribe this protein. Future work will determine whether sensory neurons from the heart express receptor proteins for other known stimulant agents such as capsaicin, prostaglandins, and bradykinin.
Brief biography: Following completion of a Ph.D. degree in physiology from the University of Wisconsin, I accepted a faculty position at the University of Kansas. I have taught introductory biology, Mammalian Physiology, Human Physiology, and Respiratory Physiology classes at KU. Currently I teach a large introductory biology course (Biology 150: Principles of Molecular and Cellular Biology) in the fall semester and the circulatory and respiratory sections of Mammalian Physiology course in the spring. Funding for our research has come principally from the American Heart Association. I am also involved in directing several federally funded grants that provide programs to increase the interest and success of minority students in the biomedical sciences. In this capacity, I serve as the Director of the KU Office for Diversity in Science Training.
- Wacker, M.J., O. Tevis, J. Hanke, T. Howard, W. Gilbert, J.A. Orr. Characterization of thromboxane A2 receptor and TRPV1 mRNA expression in cultured sensory neurons. Neuroscience Letters. 515: 12-17, 2012.
- Wacker, M.J., L.M. Kosloski, W.J. Gilbert, C.D. Touchberry, D.S. Moore, J.K. Kelly, M. Brotto, J.A. Orr. Inhibition of thromboxane A2-induced arrhythmias and intracellular calcium changes in cardiac myocytes by blockade of the IP3 pathway. J. of Pharm. and Exper. Ther. 331(3): 917-24, 2009.
- Wacker, M.J., S.R. Best, L.M. Kosloski, C.J. Stachura, R.L. Smoot, C.B. Porter, and J. A. Orr. Thromboxane A2 – induced arrthythmias in the anesthetized rabbit. Am. J. Physiol. Heart Circ. Physiol. 290: H1353-H1361, 2006.
- Wacker, M.J., J.B. Tyburski, C.P. Ammar, M.C. Adams, and J.A. Orr. Detection of thromboxane A2 receptor mRNA in rabbit nodose ganglion neurons. Neuroscience Letters. 36: 121-126, 2005.
- Wacker, M.J., H.L. Wilhelm, S.E. Gomez, E. Floor and J.A. Orr. The role of serotonin in the thromboxane A2 induced coronary chemoreflex. Am. J. Physiol. Heart Circ. Physiol. 284: H867-H875, 2003.
- Wacker, M.J., R.N. Tehrani, R.L. Smoot, and J.A. Orr. Thromboxane A2 mimetic evokes a bradycardia mediated by stimulation of cardiac vagal afferent nerves. Am. J. Physiol. Heart Circ. Physiol. 282: H482–H490, 2002.
- Murtha, Y.M., B.M. Allen, and J.A. Orr. The role of protein kinase C in thromboxane A2 - induced pulmonary artery vasoconstriction. J. of Biomedical Sci. 6: 293–295, 1999.
- Liu, F., J.-Y. Wu, D. Beasley, and J.A. Orr. TxA2 - induced pulmonary artery contraction requires extracellular calcium. Respir. Physiol. 109: 155–166, 1997.
- Kenagy, J., J. VanCleave, L. Pazdernik, and J.A. Orr. Stimulation of Group III and IV afferent nerves from the hind limb by thromboxane A2. Brain Research. 744: 175–178, 1997.
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