Dr. John DeSimone
 |
Contact Information
Dr. John DeSimone
Professor
Department of Physiology and Biophysics
Virginia Commonwealth University
P.O. Box 980551
Richmond, Virginia 23298-0551
Tel: 804-828-4489
Fax: 804-828-7382
email: jdesimon@vcu.edu |
John A. DeSimone received his undergraduate degree in Chemistry in 1964 from SUNY at Buffalo. He received his Ph.D. in Biophysics in 1971 from Harvard University under the mentorship of S. Roy Caplan. After completing postdoctoral training in Chemical Engineering at the University of Minnesota in Minneapolis, Dr. DeSimone was a research scientist in the Central Research Division of the 3M Company in St. Paul in 1973. He joined VCU in 1974.
Research
Food selection is an important factor in maintaining proper nutrition and long-term health. There are many factors that determine patterns of food selection. Among the most important of these are taste quality and intensity. There are five primary taste qualities: salty, sour, sweet, bitter, and umami. We are all familiar with the first four of these. Sweet stimuli tend to be appetitive even at high concentration. Salty stimuli are mainly appetitive except at excessively high concentration (e.g. sea water). Sour and bitter taste stimuli are normally aversive serving as a warning against ingestion of potentially toxic substances, but at low intensity and in certain special cases (salad dressing, beer, coffee) sour or bitter tastes are sometimes tolerated. Umami (savory in Japanese) describes the “meaty” taste of L-glutamate, and is commonly an appetitive taste component of meat and fish based broths.
In my lab we have concentrated our research on discovering the transduction mechanisms for the salty and sour taste qualities. As physiologists we are concerned with the biochemical events that occur in the lingual taste receptor cells when salty and sour taste stimuli flow over the tongue. From a nutritional standpoint the most important salty stimulus is sodium chloride which evokes taste sensations that are essentially purely salty. Other salts usually evoke more than one taste quality, e.g. potassium chloride tastes both salty and bitter. Work to date based on electrophysiological recordings from the taste nerves of laboratory animals and fluorescence imaging studies on isolated taste buds indicates the existence of two taste-related cation detectors in taste receptor cells. One is the sodium-specific epithelial sodium channel, ENaC, while the other is sensitive to a variety of cations and has many, but not all, of the physiological and pharmacological properties of the vanilloid receptor 1 or TRPV1. The molecular characterization of this salt taste receptor is now underway under the direction of my colleague in the Department of Physiology and Biophysics, Dr. Vijay Lyall.
All known stimuli for sour taste are acids suggesting that molecular sour taste detectors in taste receptor cells might be pH sensors. Human psychophysical studies indicate that taste receptor cells do not detect extracellular pH. Physiological studies by my colleagues and me demonstrate that taste receptor cells are intracellular pH sensors. The intensity of the neural response to acids is proportional to the decrease in intracellular pH. Adaptation to acids in taste receptor cells is achieved through a calcium-activated sodium-hydrogen exchanger. We have more recently found that the early phasic part of the neural response to acids has a transduction mechanism different from the later tonic part. This phasic part depends on a rapid cell volume decrease subsequent to a decrease in intracellular pH. We are currently investigating the mechanism by which strong acids (fully dissociated acids) cause a decrease in intracellular pH. In this regard data to date indicate a role for proton channels in a subset of sour-sensitive taste cells.
Teaching
I present cell physiology lectures to our first-year medical students, lectures on the basic physiology of vision in our graduate mammalian physiology course, and lectures on the mechanism of cell excitability and advanced topics in vision in our graduate cell physiology course. I have also directed and participated in advanced courses dealing with transduction mechanisms in sensory receptors. My lab continues to train M.S. and Ph.D. students and postdoctoral associates.
Selected Publications
Original Work
Ye, Q., Heck, G.L., and DeSimone, J.A. The anion paradox in sodium taste reception: Resolution by voltage-clamp studies. Science 254: 724-726, 1991. PubMed
Lyall, V., Alam R.I., Phan T.H., Russell O.F., Malik S.A., Heck G.L. and DeSimone J.A. Modulation of rat chorda tympani NaCl responses and intracellular Na+ activity in polarized taste receptor cells by pH. J. General Physiology, 120: 793_815, 2002. PubMed
Lyall, V., Heck, G.L., Vinnikova, A.K., Ghosh ,S., Phan ,T.H., Alam, R.I., Russell, O.F., Malik, S.A,, Bigbee, J.W., and DeSimone, J.A. The mammalian amiloride-insensitive non-specific salt taste receptor is a vanilloid receptor-1 variant. J. Physiology (London), 558: 147-159, 2004. PubMed
Lyall, V., Alam R.I., Malik S.A., Phan T.H., Vinnikova, A.K., Heck G.L. and DeSimone J.A. Basolateral Na+-H+ exchanger-1 (NHE-1) in rat taste receptor cells is involved in neural adaptation to acidic stimuli. J. Physiology (London), 556: 159-173, 2004. PubMed
Lyall, V., Pasley, H., Phan, T.H., Mummalaneni ,S., Heck, G.L., Vinnikova, A.K., and DeSimone, J.A. Intracellular pH modulates taste receptor cell volume and the phasic part of the chorda tympani response to acids. J. General Physiology 127: 15-34, 2006. PubMed
Lyall, V., Phan, T-H. T., Mummalaneni, S., Mansouri, M., Heck, G.L., Kobal, G., and DeSimone, J.A. Effect of nicotine on chorda tympani responses to salty and sour stimuli. J. Neurophysiol. 98: 1662-1674, 2007. PubMed
Review
DeSimone, J.A. and Lyall, V. Taste receptors in the gastrointestinal tract III. Salty and sour taste: sensing of sodium and protons by the tongue. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G1005-10, 2006. Epub 2006 Jun 29. PubMed
