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R B Barlow

Publications and source records attributed to R B Barlow.

At least 19 recordsLinked to original sources
PubMed1992

Inactivation of brain cortex muscarinic receptors by 4-diphenylacetoxy-1-(2-chloroethyl) piperidine mustard.

We demonstrated in this study that 4-DAMP [4-diphenylacetoxy-1-(2- chloroethyl) piperidine] mustard, which cyclizes to the aziridinium ion, behaved as a non-selective, non-competitive inhibitor of muscarinic receptors in rat brain cortex. It inactivated to the same extent the M1, M2 and M4 muscarinic receptors present in this tissue, as well as receptors accessible or not accessible to quaternary antimuscarinic drugs. Under mild incubation conditions, the muscarinic receptors in a state with super high affinity for agonists (SH receptors) were less affected by preactivated 4-DAMP mustard than the receptors in the states with lower affinity for agonists (H and L receptors).

Animals↗
PubMed1992

The Limulus-eye view of the world.

The compound lateral eye of the adult horseshoe crab, Limulus polyphemus, views the world with approximately 1000 ommatidia. Their optical properties and orientation determine the eye's resolution, field of view, and light collecting ability. Optic axes of adjacent ommatidia diverge from 1-15 deg with an average value of 5.5 deg yielding an average resolution of 0.1 cycles/deg. Resolution is not uniform across the eye: along horizontal planes, it is maximal in the anterior region of the eye (0.22 cycle/deg) and minimal in the posterior region (0.07 cycle/deg); along vertical planes, it is maximal near or just below the horizon (0.23 cycle/deg) and minimal above the horizon (0.04 cycle/deg). Together the ommatidia of one eye view approximately 60% of the hemispheric world on one side of the body. There is little binocular overlap (< 1% of total field). Ommatidial facets of up to 320 microns in diameter (among the largest known in the animal kingdom) make the eye a superb light collector. Limulus are known to use vision to find mates both day and night. Apparently, the optics of the lateral eye sample a large enough part of the world with sufficient resolution and light-collecting ability for the animal to succeed at this essential task.

Animals↗
PubMed1992

A circadian clock in the Limulus brain transmits synchronous efferent signals to all eyes.

A circadian clock in the brain of the horseshoe crab, Limulus polyphemus, has an important role in the function of the peripheral visual system. At night, the clock transmits neural activity to the lateral, ventral, and median eyes via efferent optic nerve fibers. The activity occurs in synchronous bursts (maximum rate of 2 bursts/s) with individual efferent fibers contributing a single spike in each burst. The circadian efferent activity originates in the protocerebrum. Lateral connections synchronize the efferent activity recorded from the two halves of the protocerebrum, suggesting the existence of bilateral circadian oscillators. Circadian efferent activity survives excision of the brain and isolation of the protocerebrum. We conclude that circadian clock and its complex neural circuitry are fundamental components of the Limulus visual system.

Animals↗
PubMed1992

Visual responses in teleosts. Electroretinograms, eye movements, and circadian rhythms.

We have recorded ocular potentials in response to brief flashes of light from two teleosts, the white perch (Roccus americana) and the green sunfish (Lepomis cyanellus). The animals were respired and maintained in an alert state for up to 2 d. Responses were recorded with corneal and transcleral electrodes. The responses of green sunfish were composed of electroretinogram (ERG) and eye movement potentials, whereas the responses in white perch contained only the ERG. Injection of curare abolished the sunfish eye movement potentials, unmasking the ERG. Observation under infrared illumination established a direct relationship between eye movements and the fast potentials which could be abolished by curare. We found no evidence of circadian changes in the amplitude of the ERG b-wave of either species. However, our results combined with those of a previous study of sunfish ocular potentials (Dearry, A., and B. Barlow, Jr. 1987. J. Gen. Physiol. 89: 745-770) suggest that the sunfish visual system exhibits rhythmic changes in oculomotor responses, which appear to be controlled by a circadian oscillator.

Animals↗
PubMed1992

The contribution of charge to affinity at functional (M3) muscarinic receptors in guinea-pig ileum assessed from the effects of the carbon analogue of 4-DAMP methiodide.

1. 4-Diphenylacetoxy-1:1-dimethyl cyclohexane (carbo-4-DAMP) is the carbon analogue of 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methiodide. The compounds differ only in that the quaternary nitrogen atom in 4-DAMP methiodide is replaced by a quaternary carbon atom, which is uncharged. 2. Carbo-4-DAMP appears to act competitively at functional (M3) muscarinic receptors in guinea-pig ileum. Estimates of log affinity constant are 6.0 at 30 degrees C and 5.9 at 37 degrees C, i.e. the compound has 0.1% of the affinity of 4-DAMP methobromide. 3. The absence of charge makes little difference to the conformation as determined by X-ray crystallography. The bond lengths and angles are very similar, though the bonds in the cyclohexane ring of carbo-4-DAMP are consistently slightly longer than those in the piperidinium ring of 4-DAMP methiodide, and the presence of the charge slightly reduces the space between molecules. 4. The difference between the affinities of 4-DAMP methobromide and carbo-4-DAMP indicates that the contribution of coulombic forces to the binding between 4-DAMP methiodide and muscarinic (M3) receptors is at least 17 kJ mol-1 (4.1 kcal mol-1) at 37 degrees C. How much this is an underestimate depends upon how much hydrophobic binding is greater with the uncharged compound.

Animals↗
PubMed1991

Visual performance of horseshoe crabs day and night.

A circadian clock modulates the structure and function of the lateral eyes of Limulus polyphemus, greatly increasing their sensitivity at night. During the mating season, male Limulus are visually attracted both day and night to females and objects that resemble females. This paper asks how well Limulus can see day and night, and whether the circadian changes in retinal sensitivity might influence the ability of these animals to find mates. We recorded the visual behavior of male and female horseshoe crabs in the vicinity of an object--a cement hemisphere (29.5 cm diameter) similar in size and shape to a female horseshoe crab--placed in a mating area near Mashnee Dike, Bourne, Massachusetts. Males oriented toward this target from an average distance of 0.94 m during the day and 0.88 m at night; and females appeared to avoid the target. We conclude that males can see potential mates at night almost as well as they can during the day. Apparently the circadian changes in the retina help compensate for the daily changes in illumination in the animal's normal environment. This study provides the first evidence for a role of visual circadian rhythms in an animal's natural behavior.

Animals↗
PubMed1991

The use of 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMP mustard) for estimating the apparent affinities of some agonists acting at muscarinic receptors in guinea-pig ileum.

1. 4-Diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMP mustard), which is known to block muscarinic M3 receptors in preference to muscarinic M2 receptors, was used to estimate the apparent affinity constants of some agonists acting at muscarinic receptors in guinea-pig ileum. Estimates for carbachol and n-pentyl-trimethyl ammonium iodide were similar to published values obtained in similar conditions: those for n-hexyl-trimethyl ammonium iodide were slightly lower. 2. The results for the agonists, n-pentyl- and n-hexyl-trimethyl ammonium iodides and for the partial agonist, n-heptyl-trimethyl ammonium iodide were not as regular as was suggested by Stephenson, though there is an overall increase in apparent affinity with chain length. 3. Estimates of apparent affinity may be affected by hexamethonium, usually present in experiments on ileum. Its absence had little effect on the results with carbachol but reduced the estimates obtained with n-pentyl trimethyl ammonium, which has strong nicotinic effects compared with its muscarinic effects. On ileum treated with tetrodotoxin the values for n-pentyl trimethyl ammonium were similar to those obtained in the presence of hexamethonium (0.28 mM): slightly higher estimates of affinity were obtained in the presence of indomethacin (2.8 microM). The nicotinic effects of n-pentyl ammonium may involve the release of prostaglandins. 4. The estimates of apparent affinity did not depend on the method used to calculate them as the 'null' method and the 'operational' method give similar answers. Estimates of the transducer-ratio for the partial agonist, n-heptyl-trimethyl ammonium iodide, were numerically the same as those of its efficacy. 5. This work illustrates the use of 4-DAMP mustard as a tool for measuring the apparent affinity of agonists acting at muscarinic M3 receptors.

Animals↗
PubMed1990

Some differential effects of 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride on guinea-pig atria and ileum.

4-Diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride (I) cyclizes at neutral pH to form an aziridinium salt. The formation and breakdown of the salt depend on the temperature (in the range 25 to 37 degrees C). In solution at 30 degrees C, peak levels, corresponding to 60-80% conversion, are reached after around 60 min and the half-life exceeds 100 min. In the presence of 0.9% NaCl conversion was reduced to 45-60%. I blocks muscarinic receptors in guinea-pig ileum and atria irreversibly and it is possible to produce dose-ratios on ileum with 10 nM I which are about 100 times those on atria. After about 30 min exposure to solutions of I (prepared 15-20 min previously so that formation of aziridinium ions is well-established) the graph of log (dose-ratio) against time is linear and similar plots were obtained with two different agonists, carbachol and ethoxyethyltrimethylammonium. With results for the ileum, extrapolation of the line suggests that it does not start from zero (dose-ratio = 1): this is because of an initial relatively rapid reversible block. This early phase is similar to that seen on ileum with 10 nM 4DAMP methobromide, which is a competitive antagonist, so is probably caused by competitive block by the aziridinium ion, which closely resembles 4DAMP metho-salts. The subsequent irreversible phase should be caused by alkylation of the receptors. I is easy to make and should be a valuable tool for the study of muscarinic receptors.

Animals↗
PubMed1979

Light and efferent activity control rhabdom turnover in Limulus photoreceptors.

Photosensitive membrane structures in the retinular cells of the Limulus lateral eye are broken down and renewed daily. The first light onset causes a rapid, synchronous disassembly and buildup of the rhabdom in each photoreceptor cell. The entire process is complete within 30 minutes. Blocking the efferent input to the retina from the brain blocks the turnover of the rhabdom, and mimicking the efferent input by optic nerve stimulation restores it.

Animals↗
PubMed1979

Temperature coefficients of affinity and entropies of adsorption from enantiomeric pairs of compounds acting at muscarinic receptors in the guinea-pig ileum.

1 The affinities of a series of enantiomeric pairs of esters of phenylcyclohexylglycollic acid, of a pair of esters of alpha-methyltropic acid and of hyoscyamine methiodide have been measured for the muscarinic receptors of the guinea-pig ileum at 30 degrees and 37 degrees C and estimates have been made of their free energies, enthalpies and entropies of adsorption. 2 With (-)-S-hyoscyamine methiodide the enthalpy of adsorption is negative whereas with the (+)-R-enantiomer it is positive. 3 With the esters of phenylcyclohexylglycollic acid the size of the onium group appears to be as important as the stereochemical configuration in determining entropy. Large onium groups appear to be associated with an increase in entropy though this can only be measured approximately because of the narrow range of temperature which can be used.

Adsorption↗
PubMed1979

Temperature coefficients of affinity constants for the binding of antagonists to muscarinic receptors in the rat cerebral cortex.

1 The temperature coefficients of binding of a series of muscarinic antagonists to their receptors in membrane preparations from the rat cerebral cortex has been examined. 2 At 37 degrees C the affinity constants agree with those determined by antagonism of acetylcholine-induced contractions of the guinea-pig ileum. 3 The temperature-dependence of the affinity constants is low; for the antagonists examined, the affinity constants at 0 degrees C differ by less than a factor of 3 from those measured at 37 degrees C. 4 There are qualitative similarities between the estimates of the temperature coefficient of binding of the antagonists to receptors in ileum strips and in the cerebral cortex.

Animals↗
PubMed1978

Intensity coding in primate visual system.

The pupil reflex and the discharge of LGN cells of the awake macaque were measured under stimulus conditions that yielded evidence for wide-range intensity coding in human psychophysical experiments. Ganzfeld flashes of white light were delivered under dark-adapted conditions to the surgically immobilized eye of the monkey while the other eye was observed in the infrared. Three-sec flashes elicited a consensual pupil reflex that was graded from -8 to 0 log Lamberts (L), indicating that the optic nerve fibers are capable of coding at least an 8 log-unit range of light intensity. In the physiological experiments, shorter flashes (0.1-0.5 sec) but otherwise identical conditions elicited monotonically graded responses from one type of LGN cell over the photopic range of -5 to 0 log L. Responses from other types of LGN cells were also graded over wide ranges but had different thresholds and, in some cases, nonmonotonic intensity-response functions. Latency of the excitatory LGN responses decreased with increasing intensity according to a power function with slope of-0.08. The pupil reflex and the LGN cell excitatory responses approximate power functions of light intensity with exponents of 0.22 and 0.14-0.29 respectively. The range of intensity coding found for single LGN cells is the widest yet reported for diffuse stimuli.

Animals↗
PubMed1978

Evaluation of a surgical method for immobilizing the eye of an alert monkey.

One eye of a macaque monkey was immobilized by severing the third, fourth, and sixth cranial nerves. The residual movements of the operated eye were measured by repeatedly mapping the position of a visual receptive field. Movements of several degrees were caused by contraction of the orbital musculature during the closure blink. The amount of movement was dramatically reduced by paralysis of the superficial orbital muscles with a local anesthetic. Side effects of surgical immobilization include increased risk of corneal clouding and eye infection. In one monkey intraocular pressure was lowered for several weeks. Regeneration of the severed nerves causes return of some voluntary movement of the eye, which is not coordinated with movements of the unoperated eye even after nine months postoperative survival. The suitability of this approach for studies on the visual nervous system is discussed.

Abducens Nerve↗
PubMed1978

Inhibition in the Limulus lateral eye in situ.

Inhibition in the Limulus lateral eye in situ is qualitatively similar to that in the excised eye. In both preparations ommatidia mutually inhibit one another, and the magnitude of the inhibitory effects are linear functions of the response rate of individual ommatidia. The strength of inhibition exerted between single ommatidia is also about the same for both preparations; however, stronger effects can converge on a single ommatidium in situ. At high levels of illumination of the retina in situ the inhibitory effects are often strong enough to produce sustained oscillations in the discharge of optic nerve fibers. The weaker inhibitory influences at low levels of illumination do not produce oscillations but decrease the variance of the optic nerve discharge. Thresholds for the inhibitory effects appear to be determined by both presynaptic and postsynaptic cellular processes. Our results are consistent with the idea that a single ommatidium can be inhibited by more of its neighbors in an eye in situ than in an excised eye. Leaving intact the blood supply to the eye appears to preserve the functional integrity of the retinal pathways which mediate inhibition.

Action Potentials↗
PubMed1978

Limulus ventral eye. Physiological properties of photoreceptor cells in an organ culture medium.

Ventral photoreceptor cells bathed in an organ culture medium typically have resting potentials of -85 mV and membrane resistances of 35 Momega and, when dark-adapted, exhibit large potential fluctuations (LPFs) of 60 mV and small potential fluctuations (SPFs) of less than 30 mV. LPFs appear to be regenerative events triggered by SPFs, the well-known quantum bumps. In the dark, SPFs and LPFs occur spontaneously. At intensities near threshold, the rate of occurrence is directly proportional to light intensity, indicating that SPFs and LPFs are elicited by single photon events. At higher intensities, SPFs and LPFs sum to produce a receptor potential that is graded over approximately a 9-log-unit range of light intensity. Amplitude histograms of the discrete potential waves are bimodal, reflecting the SPF and LPF populations. Histograms of current waves are unimodal. SPFs and LPFs are insensitive to 1 microgram tetrodotoxin. I-V characteristics show initial inward currents of approximately 15 nA for voltage clamps to -40 mV and steady-state outward currents for all clamp potentials. Photoreceptor cells bathed in organ culture medium retain these properties for periods of at least 75 days.

Animals↗
PubMed1978

The effects of replacing ester by amide on the biological properties of compounds related to acetylcholine.

1 Replacement of ester by amine in series of derivatives of diphenylacetic acid reduces the affinity for muscarine-sensitive acetylcholine receptors of the guinea-pig ileum from 40- to 100-fold. With similar series of phenylacetic acid the reduction is only 2- to 4-fold. In both series changes in the composition of the onium group produce similar changes in the affinity of amides and esters and it appears that the stiffness of the amide bond reduces the binding of the phenyl groups at the far end of the molecule from the onium atom. 2 Replacement of ester by amide in similar series of acetyl compounds reduces activity on the guinea-pig ileum over 1000-fold and on the frog rectus over 50-fold. Compounds with larger onium groups are antagonists on both preparations with log affinity constant around 3. The amides have similar affinity for electric eel acetylcholinesterase. 3 The amides are slightly bigger than the esters in solution and slightly more hydrophilic. 4 Replacement of ester by amide in acetylcholine reduces the proportion of gauche conformer about the C--C--bond from 100% to 39%. 5 The ability of acetylcholine to activate receptors is thought to depend on some degree of flexibility in the --CO--0--bond, though the hydration of the bond may also be important.

Acetylcholine↗
PubMed1978

The effects of a hydroxyl group on some chemical and biological properties of n-pentyl ammonium salts.

The effects of a hydroxyl group on the activity and affinity of compounds related to n-pentyltrimethylammonoum have been studied on the guinea-pig ileum, frog rectus, acetylcholinesterase and on partitioning (Rm) and size (phiov, Vm). The hydroxyl group lowered affinity in all tests, confirming the importance of hydrophobic forces in binding to receptors. Activity on the ileum was lowered appreciably but on the rectus only slightly. The effects on Rm did not indicate any interactions between hydroxyl, onium group and water but the apparent size of the hydroxyl group (deltaphiov) depends on the nature of the onium group.

Acetylcholine↗