In order for cells to perform their normal functions in the body they must interact with a whole host of substances including chemicals, proteins, and other cells. On the surface of all cells are specific receptors which are like little antennae, each one tuned to a specific substance or group of substances. These cell surface receptors constitute a large class of molecules that are present on the exterior of the cell membrane. There are several types of receptors which react to these external substances in different ways. One type of these receptors include signaling enzymes, such as receptor tyrosine kinases, and receptors for cell factors such as tumor necrosis factor (TNF), cytokines, nerve growth factor (NGF) or enzymes such as carbonic anhydrase VI (CAVI). These receptors respond to these incoming substances by forcing the cell to act in a specific manner.

Two sets of these incoming molecules which activate or inhibit cellular function depending upon their concentrations, are called cyclic AMP and cyclic GMP. These molecules are present in human saliva and are involved in the complex process of maintaining taste bud integrity and in assisting in the actual production of taste responsiveness.

We have measured cyclic AMP and cyclic GMP in saliva of normal subjects and of patients with taste loss (hypogeusia). We have also measured these substances after treatment of patients with hypogeusia with theophylline, a drug which has been successful in restoring taste function in some patients with hypogeusia. Since theophylline interferes with the breakdown or metabolism of both of these substances we would expect that treatment with theophylline would increase concentrations of both cyclic AMP and cyclic GMP in saliva since less would be broken down and more would be preserved. However, this is not always the case. This deepens the mystery as to how this drug helps patients with hypogeusia regain their taste function.

Some of this material was presented at the Experimental Biology 2003 meeting held in San Diego in April 2003. A portion of this material was recently published — Henkin, R.I., Velicu, I., Papathanissiu, Dichotomous changes in cAMP and cGMP in human parotid saliva after oral theophylline, FASEB J, 17:A1028, 2003.