SUSAN E. SENOGLES
ASSOCIATE PROFESSOR

EDUCATION:
B.S. 1977, University of Minnesota, Minneapolis-St. Paul, Minnesota
Ph.D. 1984, University of Minnesota, Minneapolis-St. Paul, Minnesota
Postdoctoral 1984-1989, Duke University Medical Center, Durham, North Carolina

RESEARCH INTEREST: Research in my laboratory focuses on the biochemistry of trans-membrane signal transduction, with particular emphasis on the dopaminergic systems. The catecholamine, dopamine, signals through several distinct subtypes of receptors, including the D1 and D2 dopamine receptors. The prototypic system for the D2 dopamine receptor is the anterior lobe of the pituitary, where the major consequence of dopamine action is the mediation of hormone release. The D2 dopamine receptor, in the anterior pituitary appears to function by activation of a complex set of intracellular signals, including inhibition of cAMP, activation of potassium channels and inhibition of calcium channels, all thought to be G protein-linked. The elucidation of the biochemical mechanisms employed by a single receptor to signal to multiple effector systems is the major goal of this project.
My laboratory is also investigating the D3 dopamine receptor, which is thought to be the site of neuroleptic action. To date, a signaling pathway has not been well-documented for the D3 dopamine receptor. My laboratory is currently using a variety of techniques, including antisense RNA and analysis of chimeric D2/D3 receptors to elucidate the functional consequences of D3 dopamine receptor activation.

CURRENT RESEARCH SUPPORT:
R29NS28811 "Signal Transduction of the D2 Dopamine Receptor Subtypes" April 1, 1991 - March, 31, 1996; $340,304 TDC.

PUBLICATIONS: (only selected publications are listed)
4. Tollefson, G.D., Senogles, S.E., Frey, S.W., Tuason, V.B., and Nicol, S.E. (1982) A comparison of peripheral and central human muscarinic cholinergic receptor affinities for psychotropic drugs. Biol. Psych., 17, 555-567.
5. Tollefson, G.D. and Senogles, S.E. (1982) A cholinergic role in the mechanism of lithium in mania. Biol. Psych., 18, 467-479.
6. Tollefson, G.D. and Senogles, S.E. (1983) A comparison of first and second generation antidepressants at the human caudate nucleus. J. Clin. Psychopharm., 3, 231-234.
7. Tollefson, G.D., Senogles, S.E. and Frey, W.H. (1983) Ionic regulation of antagonist binding to the human muscarinic cholinergic receptor of caudate nucleus. J. Psychiat. Res., 17, 275-283.
8. Senogles, S.E. and Nelsestuen, G.L. (1983) von Willebrand Factor: A protein which binds at the cell surface interface between platelets. J. Biol. Chem., 258, 12327-12333.
9. Senogles, S.E., Amlaiky, N., Johnson, A.L., and Caron, M.G. (1984) Affinity chromatography of the anterior pituitary D2 Dopamine Receptor. Biochemistry, 25, 749-753.
10. Senogles, S.E., Benovic, J.L., Amlaiky, N., Unson, C., Milligan, G., Vinitsky, R., Spiegel, A.M., and Caron, M.G. (1987) The D2 dopamine receptor of anterior pituitary is functionally associated with a pertussis toxin-sensitive guanine nucleotide binding protein. J. Biol. Chem., 262, 4860-4867.
11. Gingrich, J.A., Amlaiky, N., Senogles, S.E., Chang, W.K., McQuade, R.D., Berger, J.G., and Caron, M.G. (1988) Affinity chromatography of the D1 dopamine receptor from rat corpus striatum. Biochemistry, 27, 3907-3912.
12. Senogles, S.E., Amlaiky, N., Falardeau, P.F., and Caron, M.G. (1988) Purification and characterization of the D2 dopamine receptor from bovine anterior pituitary. J. Biol. Chem., 263, 18996-19002.
13. Gingrich, J.A., Senogles, S.E., Amlaiky, N., Chang, W.K., Berger, J.G., and Caron, M.G. (1988) Isolation and biochemical characterization of the D1 and D2 dopamine receptor. In F.F. Hefti and W.J. Weiner (Eds.), Progress in Parkinson Research (pp. 67-76). New York: Plenum Press.
14. Senogles, S.E., Amlaiky, N., Berger, J.G., and Caron, M.G. (1988) Biochemical properties of the D1 and D2 dopamine receptors. In M. Goldstein, K. Fuxe, and I. Tabachnik (Eds.), Central D1 Dopamine Receptors Vol. 235 (pp. 33-42). Plenum Publishing Co. Advances in Experimental Medicine and Biology.
15. Senogles, S.E. and Caron, M.G. (1988) Characterization of the endogenous G-Protein which co-purifies with the D2 dopamine receptor. In P.F. Spano, G. Biggio, G. Toffano, and G.L. Gessa (Eds.), Central and Peripheral Dopamine Receptors: Biochemistry and Pharmacology (pp. 7-14). Symposia in Neurosciences, Fidia Research Series, Vol. 5. Springer-Verlag Padoa: Liviana Press.
16. Caron, M.G., Senogles, S.E., Amlaiky, N., and Berger, J.B. (1988) D1 and D2 dopamine receptors: Identification by photoaffinity labeling and purification by affinity chroma-tography. In P.M. Beart and D.M. Jackson (Eds.), Dopamine Systems and Their Regulation.
17. Raymond, J.R., Fargin, A., Lohse, M.J., Regan, J.W., Senogles, S.E., Lefkowitz, R.J., and Caron, M.G. (1989) Identification of the ligand binding subunit of the human 5-HT1A receptor with [125]N3-NAPS. Mol. Pharmacol, 36, 15-21.
18. Senogles, S.E., Spiegel, A.M., Padrell, E., Iyengar, R., and Caron, M.G. (1990) Specificity of receptor G protein interactions: Discrimination of Gi subtypes by the D2 dopamine receptor in a reconstituted system. J. Biol. Chem., 265, 4507-4514.
19. Bates, M.D., Gingrich, J.R., Bunzow, J.R., Falardeau, P., Dearry, A., Senogles, S.E., Civelli, O., and Caron, M.G. (1990) Molecular characterization of the dopamine receptors. Am. J. of Hypertension, 3, 295-335.
20. Anderson, P.H., Gingrich, J.A., Bates, M.D., Dearry, A., Falardeau, P., Senogles, S.E., and Caron, M.G. (1990) Dopamine receptor subtypes: Beyond the D1/D2 classification trends. Pharmacological Sciences, 11, 231-236.
21. Bates, M.D., Senogles, S.E., Bunzow, J.R., Liggett, S.B., Civelli, O., and Caron, M.G. (1991) Regulation of responsiveness at D2 dopamine receptors by receptor desensitization and adenylyl cyclase sensitization. Molecular Pharmacology, 39, 55-63.
22. Senogles, S.E. (1994) The D2 dopamine receptor mediates inhibition of growth in GH4ZR7 Cells: Involvement of protein kinase CE. Endocrinology, 134, 783-789.
23.Senogles, S.E. (1994) The D2 dopamine receptor isoforms signal through distinct Gi a proteins to inhibit adenylyl cyclase: A study with site-directed mutant Gi a proteins. J. Biol. Chem., 269, 23120-23127.
24. Senogles, S.E. (1995) Defining specificity of G protein and receptor interactions by use of site-directed mutants of Gi a subunits. In M.A. Ariano and D.J. Surmerer (Eds.), Molecular and Cellular Mechanisms of Neostriated Function (pp. 103-110). Austin: R.G. Landes Company.
25. Dahmer, M.K. and Senogles, S.E. (1996) Dopaminergic inhibition of catecholamine secretion from chromaffin cells is mediated by D4 and D5 dopamine receptors. J. Neurochem., in press.
26.Senogles, S.E. and Quasney, M.W. (1996) Use of transfection techniques to study the function of D2 dopamine receptors. In J. Thomas (Ed.), Endocrine Reviews. New York: Academic Press, in press.