A commonly observed phenomenon in biological systems is the waning of response amplitude when the stimulus signal is continuously present. This phenomenon was first observed in sensory systems where it was called adaptation, and later was noted to be a common feature of drug, neurotransmitter and hormone receptors where it is known as desensitization. Adaptation and desensitization are similar effects, one occurring at the systems level and one at the cell-molecular level of organization. It now seems probable that common mechanisms may have developed in both sensory and other receptor systems for mediating this effect. The olfactory receptor neuron is a unique model system for understanding both effects beacuse it respnds to envirnmental stimuli (sensory function) and these stimuli are chemical in nature (pharmacological ligand-receptor frunction). Recently we have shown that olfactory transduction is mediated by a second messenger system similar to those operating in phototransduction and in - adrenergic receptor mediated signal transduction. In analogy with these systems, one of the several steps in this enzyme cascade may be the molecular site of an adaptation feed-back link in olfactory receptor neurons. The entrance of Calcium ions during the odor response also suggests a possible role for Ca in producing desensitizations. The methods to be employed include whole cell patch clamp recordings of the ion currents generated by exposure to odors in single receptor neurons. The effect on these currents of various pharmacological events which interact with component enzymes in the second messenger cascade will indicate the likely site(s) and mechanism(s) underlying adaptation. Additionally single channel recording methods will be used to measure the activity of cAMP gated channels under conditions which are hypothesized to activate and inactivate this channel. Mechanisms by which signal transducing systems are modulated is a question of general relevance in cell biology and is of unique interest in the olfactory system where adaptation plays an important physiological and behavioral role for the organism. At the molecular level desensitization is an important factor limiting the clinical efficacy of drugs delivered for long periods. If, as we postulate. common mechanisms underlie this widespread biological phenomenon, then a mechanistic appreciation is essential to devising interventions which either increase or decrease response adaptation.
