Oliver M Brown, PhD
- Associate Professor of Pharmacology
Education & Fellowships
- Postdoctoral Fellow: Mount Sinai School of Medicine, New York
- PhD: Kansas State University, 1970
- Synaptic Mechanisms; Autonomic Innervation; Heavy Metal Toxicity
Synaptic Mechanisms Involved in Autonomic Control and Heavy Metal Toxicity.
We have been studying various aspects of the autonomic (particularly parasympathetic) innervation and control of the mammalian heart. Our studies on the content and dynamics of cardiac acetylcholine (ACh) have been bringing us closer to the unsolved problems related to ACh functional pools and release mechanisms. We have employed a direct chemical approach which allows for the specific determination of cardiac choline (Ch) and ACh. We have used these methods to describe the patterns of distribution of ACh in mammalian heart, and have provided evidence for parasympathetic innervation of the mammalian ventricle and a non uniform distribution of pre-ganglionic parasympathetic innervation of the heart. We have demonstrated a mechanism capable of attenuating the heart rate response to vagal stimulation that involves presynaptic alpha1 adrenergic receptor inhibition of ACh release. We have also developed a new mathematical model to describe ACh turnover kinetics.
We are studying mechanisms of synaptic events, including neurotransmitter release, and the mechanisms of heavy metal ions in inhibiting stimulus-response coupling in a unique model system, the electric organ in the tail of the little skate, Raja erinacea (an elasmobranch marine fish). The approach is to make quantitative correlations between the changes in physiology, neurochemistry, and ion movemenmt resulting from exposure to heavy metal ions in a single physiologically functioning organ preparation. Thus far, we have characterized the evoked electrical discharge, neuotransmitter (ACh) release, and Ca uptake in Raja electric organ; characterized the pre synaptic and post-synaptic Ca channels in this organ; and determined that heavy metal ions act on the pre-synaptic membrane to inhibit evoked ACh release.
O.M. Brown: Cat heart acetylcholine: Structural proof and distribution. Am. J. Physiol. 231:781-785, 1976.
P.A. McGrattan, J.H. Brown and O.M. Brown: Parasympathetic effects on the in vivo rat heart can be regulated through an a1-adrenergic receptor. Circ. Res. 60:465-471, 1987.
O. M. Brown and J. S. Andrake: Cadmium inhibits stimulus-response coupling in skate (Raja erinacea) electric organ. Comp. Biochem. Physiol. - Part C - (Comp. Pharmacol. Toxicol.) 102C:439-446, 1992.
O. M. Brown: "Autonomic Pharmacology", "Cholinergic Agonists", "Cholinergic Antagonists: Antimuscarinic and Antinicotinic Drugs", "Adrenergic Drugs", "Adrenergic Antagonists"; in: Essentials of Pharmacology (ed. C.M. Smith and A.M. Reynard), W.B. Saunders Company, Philadelphia, pp 46-91 1995.
M. E. Kriebel, B. Keller, G. Q. Fox, and O. M. Brown: Porocytosis: The fusion pore array hypothesis of transmitter release. Cell Biology International, In Press, 2000.