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PH.D. University of British Columbia |
My interest is in the neuropharmacology of the enteric nervous system (ENS) and the role of enteric nerves in the control of gastrointestinal function. The ENS consists of the myenteric plexus and the submucous plexus, both of which are ganglionated and which control motor activity and secretory activity respectively. The ENS, which contains about the same number of neurons as the spinal cord, displays considerable information processing capability and is thus a useful model with which to study the neurochemistry of various mediators, their co-localization and co-release, as well as the factors which regulate mediator release from nerve endings. Work in my laboratory has recently focussed on understanding the actions of inhibitory mediators such as adenosine and serotonin (5-HT). Both of these compounds inhibit the release of Acetylcholine and Substance P, the major excitatory mediators in the ENS. We have studied this inhibition and have characterized the receptors responsible, as well as demonstrating their locus on enteric nerve terminals. We are currently interested in the possible neuroprotective functions of adenosine at the ENS which would serve to protect enteric neurons from damage due to intestinal ischemia and subsequent reperfusion. This is an important area of morbidity and is also of concern during transplantation. We have recently demonstrated, using a functional approach, the existence of an inverse graded relationship between endogenous adenosine levels and the prevailing tissue oxygen tension. The ability of this adenosine to protect enteric nerves from the consequences of mesenteric ischemia to motor function is presently being pursued.
Xia Y, Rajapurohitam V, Cook MA, Karmazyn M. Inhibition of phenylephrine induced hypertrophy in rat neonatal cardiomyocytes by the mitochondrial KATP channel opener diazoxide. J Mol Cell Cardiol. 2004 Nov;37(5):1063-7. Gan XT, Rajapurohitam V, Haist JV, Chidiac P, Cook MA, Karmazyn M. Inhibition of phenylephrine- induced cardiomyocyte hypertrophy by activation of multiple adenosine receptor subtypes. J Pharmacol Exp Ther. 2005 Jan;312(1):27-34. Epub 2004 Sep 27. Hoque N, Cook MA, Karmazyn M. Inhibition of alpha(1)-adrenergic-mediated responses in rat ventricular myocytes by adenosine A(1) receptor activation: role of the K(ATP) channel. J Pharmacol Exp Ther. 2000 Aug;294(2):770-7.
