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My laboratory is studying mechanisms of cardiovascular regulation with a major emphasis on the brain. We focus primarily on the renin angiotensin system (RAS) of the brain. However, we are also studying other transmitter/hormone systems in the brain that affect the cardiovascular system. We are studying angiotensin II (Ang II) receptors using pharmacological (radioligand binding), anatomical (receptor autoradiography, stereotaxic surgery, immuno-cytochemistry, in situ hybridization), neurochemical (selective neurotoxin administration, radio-immunoassay, transmitter quantitation), and physiological (blood pressure, water consumption, estrous cycle) techniques.
The experimental questions under investigation are: What is the role of Angiotensin III in the brain? What is the signal transduction mechanism for AT1 angiotensin receptors in the brain. Does angiotensin I have direct effects on the brain? What is the role of brain angiotensins in reproductive function? How does Ang II interact with other neurotransmitters in the brain? Are there additional Ang II receptor subtypes in the brain and other tissues that can be identified using specific Ang II drugs and analogs?
In addition, we are examining the precise anatomical localization of Ang II receptor binding sites in the brain and other tissues.
In addition, our laboratory is screening natural products for interactions with the cardiovascular system and the central nervous system. This is being done in collaboration with scientists here at the
National Center for Natural Products Research who have considerable expertise in natural products chemistry and have generated a large repository of compounds of potential pharmacological importance.
Biographical
Information
Robert C. Speth, Professor and Chair, studied biology and psychology as an undergraduate at Western Maryland College (B.A., 1968). He went on to study physiological psychology at Connecticut College (M.A., Psychology, 1972), and psychopharmacology at Vanderbilt University (Ph.D., Pharmacology, 1976). He received postdoctoral training in receptor pharmacology in the laboratory of Dr. Henry Yamamura at the University of Arizona from 1976 to 1979. Dr. Speth was promoted to research assistant professor of Pharmacology at the University of Arizona in 1979. Dr. Speth joined the Research Division of the Cleveland Clinic as an associate staff member in 1979. In 1984 Dr. Speth moved to Washington State University to become an associate professor, then Professor of Pharmacology in the Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology in the College of Veterinary Medicine and the Pharmacology/Toxicology Program in the College of Pharmacy and a faculty member of the Center for Reproductive Biology. In 1990 Dr Speth was a visiting scientist at the National Institutes of Health, in the laboratory of Dr. Kevin Catt. From 1999-2000 Dr. Speth was a visiting scientist at the Oregon Regional Primate Research Center, Oregon Health & Science University in the laboratory of Dr. Susan Smith. He continues to be an Adjunct Professor of Physiology and Pharmacology at OHSU. Dr Speth assumed the Chairmanship of the Department of Pharmacology in the School of Pharmacy at the University of Mississippi in July, 2003.
Selected
Publications
Recent publications, selected from a total of 156 refereed and non-refereed publications since 1972.
Speth, RC, Smith, MS, & Grove, KL. 2001 Lactation decreases angiotensinogen mRNA expression in the mid-caudal arcuate nucleus of the rat brain. Am. J. Physiol.280: R1169-76.
Szabo, Z, Speth RC, Brown PR, Kerenyi L, Kao PF, Mathews WB, Ravert HB, Hilton J, Rauseo P, Dannals RF, Zheng W, Lee S, & Sandberg K. 2001. Use of positron emission tomography to study AT1 receptor regulation in vivo. J Am Soc Nephrol 12:1350-8.
Speth
RC, Smith MS, & Brogan RS. 2001. Regarding the Inadvisability of
Administering Postoperative Analgesics in the Drinking Water of Rats
(Rattus norvegicus). Contemp Top Lab Anim
Sci.40:15-7.
Gardi, J,
Krueger, JM, & Speth RC. 2002. Preparation and a simple
one-step purification of [His1-mono-125I-Tyr10,Nle27]-hGHRH(1-32)-NH2.J Labeled Cpd Radiopharm 44: 1-6.
Speth, RC, Smith,MS & Grove, KL. 2002. Brain angiotensinergic mediation of enhanced water consumption in lactating rats. Am J. Physiol. 282: R695-701.
Bagby S,
LeBard, LS, Luo, Z, Speth RC, Ogden BE, & Corless C. 2002 Ang
II AT1 and AT2 receptors in conduit arteries of normal developing
microswine. Atherosclerosis Thrombosis and Vascular Biology
22:1113-1121.
Booz GW, Day
JNE, Speth RC, & Baker KM. 2002 Cytokine G-protein signaling
crosstalk in cardiomyocytes: attenuation of Jak-STAT activation by
endothelin-1. Mol Cell Biochem. 240: 39-46.
Speth
RC. Ignore lies about animal research. The Physiologist
2002, 45 (6): 491.
Wright JW,
Tamura-Myers E, Wilson WL, Roques BP, Llorens-Cortes C, Speth
RC, & Harding JW. Conversion of brain angiotensin II to
angiotensin III is critical for pressor response in rats. Am. J.
Physiol. 2003, 284:R725-33.
Santos RAS, Simoes e Silva AC, Denise M.R. Silva, DMR, Maric
C, Speth R, Machado RP, de Buhr I, Pinheiro SVB, Lopes
MT, Mendes EP, Bader M, Lemos VS, Schultheiss H-P, Campagnole-Santos
MJ, & Walther T. Angiotensin-(1-7) is an
endogenous ligand for the G protein-coupled receptor Mas.
Proc Natl Acad Sci, USA. 2003, 100: 8258-63.
Speth
RC. The Genome Poem. Am J Med Genet. 2003. 120A (2): 3.
Speth,
RC, Smith, MS & Grove, KL. 2001 Lactation decreases
angiotensinogen mRNA expression in the mid-caudal arcuate nucleus of
the rat brain. Am. J. Physiol. 280: R1169-76.
Szabo, Z,
Speth RC, Brown PR, Kerenyi L, Kao PF, Mathews WB, Ravert HB,
Hilton J, Rauseo P, Dannals RF, Zheng W, Lee S, & Sandberg K. 2001.
Use of positron emission tomography to study AT1 receptor regulation
in vivo. J Am Soc Nephrol 12:1350-8.
Speth RC, Brown TE, Barnes, RD & Wright JW, 2003. Brain angiotensinergic activity: the state of our current knowledge. Proc. West. Pharm. Soc. 46: 11-15.
McPherson EA, Luo, Z, Brown RA, LeBard LS, Corless CC, Speth RC, & Bagby SP. 2004 Chymase-like Ang II-generating activity in end-stage human autosomal dominant polycystic kidney disease (ADPKD). J Am. Soc. Nephrol. 15:493-500.
Swenson SJ, Speth RC, & Porter JP. 2004 The Effect of a Perinatal High-Salt Diet on Blood Pressure Control Mechanisms in Young Sprague Dawley Rats. Am. J. Physiol Regul Integr Comp Physiol. 286: R764-70.
Wang G, Anrather J, Huang J, Speth RC, & Pickel VM, 2004 Iadecola C. NADPH Oxidase Contributes to Angiotensin II Ca2+ Signaling in the Nucleus Tractus Solitarius. J. Neurosci. 24: 5516- 5524.
Falcon BL, Bourassa E, Stewart J, Katovich MJ, Walter G, Speth RC, Sumners C, & Raizada MK, 2004 Angiotensin II Type 2 Receptor Gene Transfer Elicits Cardioprotective Effects in an Angiotensin II infusion Rat Model of Hypertension. Physiological Genomics, 19: 255-261
Glass M, Speth RC, Pickel V, & Iadecola C. 2005 Angiotensin II AT-1A Receptor Immunolabeling in Rat Medial Nucleus Tractus Solitarius Neurons: Subcellular Targeting and Relationships with Catecholamines. Neuroscience. 130:713-23.
Bugarith K, Dinh TT, Li, A-J, Speth RC, & Ritter, S 2005 Basomedial hypothalamic injections of neuropeptide Y-saporin (NPY-SAP) selectively disrupt hypothalamic controls of food intake. Endocrinology 146:1179-91.
Speth
RC, Kim K-H, Elton TE, & Simasko S 2005. Sarcosine1, isoleucine8
angiotensin II is an AT1 angiotensin II receptor subtype
selective ligand. Endocrine, 26: 83-88.
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