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The Piascik Lab Current Projects: We are interested in the regulation of cardiovascular function by
subtypes
of the alpha1-adrenergic receptors . These receptors
are members of the
super family of G-protein coupled receptors. Research techniques used in
the lab are whole animal cardiovascular measurements in both rats and
genetically altered mice,
in vitro assessment of contractile function, measurement of growth
responses,
immunocytochemistry and laser scanning confocal microscopy. Currently
there are 3 known subtypes of the alpha1-AR: the alpha1A,
the alpha1B and the alpha1D. While working with
Drs. Robert Graham and Dianne Perez, Dr.
Piascik participated in the cloning and characterization of the alpha1A
and the alpha1D-AR
subtypes. Over the past several years we have focused on the
regulation of peripheral vascular function by the alpha1-ARs subtypes. This
work is summarized in several recent papers. (Refer to Piascik 1995,
1997;
Hrometz 1999) It is our hypothesis that, while all blood vessels
express all
receptors, a single receptor participates in contractile regulation.
Furthermore, this regulatory receptor is different in different vascular
beds. We believe that the alpha1a
and the alpha1d-ARs are
primarily involved in the
regulation of vascular smooth muscle contraction. We have also shown
that the alpha1-ARs are
expressed in different cellular compartments
and differ in the rate and extent of agonist mediated internalization.
We
propose that these differences in cellular localization result in
different
regulatory activities for the alpha1-ARs. We believe that the
major regulatory
activity of the alpha1b-AR is in the regulation of
hypertrophic growth
responses. In collaboration with Dr. Dianne M. Perez of the Lerner
Research Institute at the Cleveland Clinic we have examined growth
responses in mice genetically altered to overexpress the wild-type and
constitutively active forms of the alpha1b-AR. These mice
develop cardiac
hypertrophy. Our preliminary studies show that these mice also have
elevated levels of the mitogen activated protein kinases (MAPK) ERK and
JNK. Therefore, we propose that these kinases link the alpha1b-AR
to hypertrophic
responses.
Chalothorn D, McCune DF, Edelmann SE, Tobita K, Keller BB, Lasley RD, Perez DM, Tanoue A, Tsujimoto G, Post GR and Piascik MT. (2003) "Differential cardiovascular regulatory activities of the alpha 1B- and alpha 1D-adrenoceptor subtypes." J Pharmacol Exp Ther. 305:1045-53. Yun J, Zuscik MJ, Gonzalez-Cabrera P, McCune DF, Ross SA, Gaivin R, Piascik MT and Perez DM. (2003) "Gene expression profiling of alpha(1b)-adrenergic receptor-induced cardiac hypertrophy by oligonucleotide arrays." Cardiovasc Res. 57:443-55. Chalothorn D, McCune DF, Edelmann SE, Garcia-Cazarin ML, Tsujimoto G and Piascik MT. (2002) Differences in the Cellular Localization and Agonist-Mediated Internalization Properties of the alpha(1)-Adrenoceptor Subtypes. Mol Pharmacol 61:1008-16. Waldrop, B.A., Piascik, M.T. and Post, G.R. (2002) Regulation of cell growth and MAPK family members ERK, JNK, and p38 kinase by the Alpha-1B and Alpha-1D adrenergic receptor subtypes. J Pharmacol Expt Ther 300:83-90. Piascik, M.T. and Perez, D.M. (2001) Perspectives in a1-adrenergic receptors: Pharmacology, Function and Future Directions., Invited Review, Perspectives in Pharmacology, J Pharmacol Expt Ther 298:403-410. Zuscik, M.J., Chalothorn, D., Hellard, D.,
Deighan, C. McGee, A., Daly, C.J., Waugh, D.J.J., Ross, S.A., Gaivin, R.J.,
Morehead, A.J., Thomas, J.D., Plow, E.F., McGrath, J.C., Piascik, M.T.,
and Perez, D.M. (2001) Hypotension,
autonomic failure, and cardiac hypertrophy in transgenic mice
over-expressing the alpha1B-adrenergic receptor. J
Biol Chem 276:13738-13743. Hrometz SL, Edelmann SE, McCune DF, Olges JR,
Hadley RW, Perez DM and Piascik MT. (1999) Expression
of Multiple alpha1-Adrenoceptors on Vascular Smooth Muscle:
Correlation with the Regulation of Contraction.
J Pharmacol Exp Ther 290: 452-463. Abstracts and Presentations: Chalothorn, D., McCune, D.F., Edelmann, S.E., Tsujimoto, G., and Piascik, M.T. Differences in cellular localization and agonist mediated internalization properties of the alpha1-adrenoceptor subtypes. Experimental Biology, 2001, Orlando, FL, April, 2001. Chalothorn, D., McCune, D.F., Edelmann, S.E., Zuscik, M.J., Perez, D.M., and Piascik, M.T. The effect of overexpression of wild-type and constitutively active alpha1B-adrenoceptors on blood pressure regulation and vascular smooth muscle contraction. 73rd Scientific Sessions of the American Heart Association, New Orleans, LA, November, 2000. McCune, D.F., Edelmann, S.E., Olges, J.R., Waldrop, B.A., Waugh, D.J., Perez, D.M., and Piascik, M.T. Regulation of the cellular localization of alpha1B and alpha1D-adrenoceptors by agonists and inverse agonists. 72nd Scientific Sessions of the American Heart Association, Atlanta, GA, November, 1999. McCune, D.F., Post, G.R., Hrometz, S.L., Edelmann, S.E., Olges, J.R., and Piascik, M.T. Subcellular co-localization of alpha1-adrenergic receptor (AR) subtypes and G-protein " subunits in vascular smooth muscle and cardiac myocytes. Experimental Biology, ‘99, Washington, D.C., April, 1999.
Current members of the Lab Michael
T. Piascik
Where are they now? - Former members of the lab: Dan Chalothorn - University of North Carolina - Chapel Hill, Postdoctoral Fellow in James Faber's lab Dan F. McCune - Cleveland Clinic, Postdoctoral Fellow in Dianne Perez' lab Sandra L. Hrometz - Ohio Northern University, Assistant Professor of Pharmacy
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