Transcript Nasal Chemesthesis: The Effect on Respiration of n

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
[email protected]
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.
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).
Thermistor
wire
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.
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
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 stimulusmediated 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.
100:8981-8986.
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.
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.
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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:
6504-6509.