NASAL CHEMESTHESIS: THE EFFECT ON RESPIRATION OF n-ALIPHATIC ALCOHOLS

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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
27109 stowrc5_at_wfu.edu
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.
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.
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 Ringers solution. Stimuli
consisting of n-aliphatic alcohols (C2-C7) and
cycloketones (C5-C7) (1.0 ml) were injected into
the flow of Ringers (10 ml/min), which was
allowed to drip from the rats 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.
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.
1008981-8986. 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. 67 478-490. Wick MJ,
Mihic SJ, Ueno S, Mascia MP, Trudell JR,
Brozowski SJ, Ye Q, Harrison NL, and Harris RA.
(1998) Mutations of ?-aminobutyric acid and
glycine receptors change alcohol cutoff
Evidence for an alcohol receptor?. Pharmacology.
95 6504-6509.
Figure 1. Experimental setup. Stimuli (1.0 ml)
were delivered via a syringe into Ringers
solution flowing through the rats 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 Ringers
solution. Figure 4. Concentration-recovery
time curve for the cycloketones tested at
concentrations ranging from 10mM to 200mM.