Substances known to alter cyclic nucleotide levels in cells were applied to the isolated toad retina and effects on rod electrical and adaptive behavior were studied. The retina was continually superfused in control ringer’s or ringer’s containing one or a combination of drugs, and rod activity was recorded intracellularly. Superfusion with cGMP, Bu(2)GMP, isobutylmethylxanthine (IBMX; a phosphodiesterase inhibitor), or PGF(2α) (a prostaglandin) caused effects in rods that closely match those observed when extracellular Ca(2+) levels were lowered. For example, short exposures (up to 6 min) of the retina to these substances caused depolarization of the membrane potential, increase in response amplitudes, and some changes in waveform; but under dark-adapted or partially light-adapted conditions receptor sensitivity was virtually unaffected. That is, the position of the V-log I curve on the intensity axis was determined by the prevailing light level, not by drug level. These drugs, like lowered extracellular Ca(2+), also decreased the period of receptor saturation after a bright-adapting flash, resulting in an acceleration of the onset of membrane and sensitivity recovery during dark adaptation.
Long-term (6-15 min) exposure of a dark-adapted retina to 5 mM IBMX or a combination of IBMX and cGMP caused a loss of response amplitude and a desensitization of the rods that was similar to that observed in rods after a long-term low Ca(2+) (10(-9)M) treatment. Application of high (3.2 mM) Ca(2+) to the retina blocked the effects of applied Bu(2)cGMP. PGE(1) superfusion mimicked the effects of increasing extracellular Ca(2+). The results show that increased cGMP and lowered Ca(2+) produce similar alterations in the electrical activity of rods. These findings suggest that Ca(2+) and cGMP are interrelated messengers. We speculate that low Ca(2+) may lead to increased intracellular cGMP, and/or that applied cGMP, and/or that applied cGMP may lower cytosol Ca(2+), perhaps by stimulating Ca(2+)- ATPase pumps in the outer segment.
Several fundamental questions remain enigmatic concerning human olfactory
sensitivity, including (i) whether detection threshold differences exist
between the two sides of the nose (and, if so, whether such differences are
influenced by handedness) and (ii) whether bilateral (i.e. binasal)
stimulation leads to lower thresholds than unilateral stimulation (and, if
so, whether the degree of facilitation is inversely related to general
olfactory ability). In this study, and well-validated single staircase
procedure was used to establish bilateral and unilateral detection
thresholds for the cranial nerve I stimulant phenyl ethyl alcohol in 130
right- and 33 left-handed subjects. No differences in sensitivity between
the left and right sides of the nose were observed in either group.
Bilateral thresholds were lower, on average, than unilateral thresholds
when the latter were categorized in terms of left and right nares. However,
the bilateral thresholds did not differ significantly from those of the
side of the nose with the lower threshold. Overall smell ability, as
measured by the University of Pennsylvania Smell Identification Test, did
not interact with any of the test measures. These data imply that (i) the
left and right sides of the nose do not systematically differ in detection
threshold sensitivity for either dextrals or sinistrals and (ii) if central
integration of left:right olfactory threshold sensitivity occurs, its
effects do not exceed the function of the better side of the nose.
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