NASAL CHEMESTHESIS: THE EFFECT ON RESPIRATION OF n-ALIPHATIC ALCOHOLS AND CYCLOKETONES DELIVERED TO THE NASAL CAVITY IN SOLUTION Atul K. Mehta, Robert C. Stowe Department of Biology, Wake Forest University, Winston-Salem, NC Methods Rats were anesthetized with urethane (ethyl carbamate: 1 g/kg injected i.p.). Two cannulae were inserted into the trachea of each rat. One cannula allowed the rat to breathe room air. The second cannula, inserted into the nasopharynx, was connected via a pump to a reservoir containing Ringer’s solution. Stimuli consisting of n-aliphatic alcohols (C2-C7) and cycloketones (C5-C7) (1.0 ml) were injected into the flow of Ringer’s (10 ml/min), which was allowed to drip from the rat’s nose. Concentrations are reported for the injected solutions. Rats were restrained in a head holder and a thermistor wire connected to an amplifier was placed into the breathing cannula. Using the Acqknowledge ® software, the respiration rates were recorded and saved for later analysis on an IBM computer. Data were analyzed by determining the time from stimulus- mediated respiratory depression until a return to the baseline rate of respiration. Introduction Chemesthesis is the sense of irritation caused by chemicals. Chemesthesis in the nasal and oral cavities is mediated by the trigeminal nerve. When the trigeminal nerve is stimulated by sensory irritants, the breathing pattern is often altered. As the lipid solubility of the irritant increases (as with increasing carbon chain length in a homologous series), the trigeminal nerve threshold decreases. As this threshold decreases, greater would be the effects upon respiration. In the present study, the effects of increasing molecular weight and concentration of a homologous series of n-aliphatic alcohols (C2-C7) and cycloketones (C5-C7) were compared to the recovery times (in seconds) required to achieve a normalized breathing pattern after stimulus presentation. Literature Cited Finger TE, Böttger B, Hansen A, Anderson KT, Alimohammadi H, and Silver WL. (2003) Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. PNAS. 100: Vijayaraghavan R, Schaper M, Thompson R, Stock MF, and Alarie Y. (1993) Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract. Archives of Toxicology. 67: Wick MJ, Mihic SJ, Ueno S, Mascia MP, Trudell JR, Brozowski SJ, Ye Q, Harrison NL, and Harris RA. (1998) Mutations of γ-aminobutyric acid and glycine receptors change alcohol cutoff: Evidence for an alcohol receptor?. Pharmacology. 95: Conclusions The alcohols tested produced recovery times that increased with lipid solubility up until a potential alcohol cutoff point, defined to be the point where potency of the alcohol no longer increases with increasing carbon length (Wick et al, 1998). The cutoff point was found to be at pentanol. The cycloketones tested produced recovery times that increased with lipid solubility with no cutoff point clearly exhibited. The cutoff point is possibly due to the physical dimensions of the binding site or receptor of alcohol, where pentanol is the largest alcohol able to fully bind (Wick et al, 1998). Alcohols and cycloketones stimulate the trigeminal nerve endings, which extend into the nasal passages and the larynx, causing reflexes which close the epiglottis and possibly induce airway constriction, leading to the breathing patterns observed after injection (Finger et al, 2003; Vijayaraghavan et al, 1993). Future experiments may examine more cycloketones in order to identify a cutoff point, as well as clarifying the cutoff point for alcohols. Figure 1. Experimental setup. Stimuli (1.0 ml) were delivered via a syringe into Ringer’s solution flowing through the rat’s nose via a nasopharyngeal cannula. Respiratory effects were detected with a thermistor wire inserted into the breathing cannula connected to an amplifier and a computer. Figure 2. Examples of respiratory changes produced by stimuli at different concentrations. Figure 3. Concentration-recovery time curve for the n-aliphatic alcohols tested at concentrations ranging from 100 mM to 4000 mM. Higher number carbon alcohols could not be tested at higher concentrations due to nonpolar properties that made it difficult to dissolve in Ringer’s solution. Figure 4. Concentration-recovery time curve for the cycloketones tested at concentrations ranging from 10mM to 200mM. Thermistor wire