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M Hanani

Publications and source records attributed to M Hanani.

At least 73 records · Page 4Linked to original sources

Synaptic activity of myenteric neurons in tissue culture.

Intracellular recordings were made from myenteric neurons of the guinea-pig caecum grown in tissue culture. The experiments were carried out on cultures older than 15 days, in which the neurons formed ganglion-like aggregates with many interconnecting nerve fibres. Intracellular injection of horseradish peroxidase demonstrated that the neurons project processes both within and outside the aggregates. Spontaneous activity was recorded in about 50% of the cells. This activity was composed of depolarizing potentials 2-20 mV in amplitude, and in most cases 10-20 ms in duration. In some instances, the potentials occurred in short bursts. The spontaneous potentials appear to be nicotinic cholinergic excitatory postsynaptic potentials (EPSPs). Electrical stimulation of the connecting fibers elicited in the neurons nicotinic cholinergic EPSPs, since they were blocked by hexamethonium. By varying the stimulus intensity and by stimulating several fibers, it was shown that the neurons are multiple-innervated. During repetitive presynaptic stimulation at frequencies above 10 Hz, there was a progressive reduction of the EPSP amplitude. It is concluded that the cultured myenteric neurons retain many of the characteristics found in the freshly isolated preparation and may be useful for studying the synaptic properties of these cells.

Animals↗

Animal model for the study of internal anal sphincter activity.

This paper describes a simple and reliable model for studying the internal anal sphincter (IAS) in the rat. The activity of the sphincter was recorded by a two-balloon system. The compliance of the balloon allowed measurements of pressure changes lower than 0.1 cm H2O. The anatomical and physiological characteristics of the rat IAS were found to be in many aspects similar to those found in the human. The rectoanal reflex in the rat consists of relaxation followed by contraction. The threshold for this response is 0.4-0.6 ml of air. The response of the IAS to prolonged rectal distension showed adaptation in 50% of the animals. Intraarterial application of drugs produced rapid, dose-dependent and reproducible effects on the IAS. The results described in this work show that the rat is a useful and convenient model for studying anal function. It may be used to investigate both the physiology and pharmacology of the IAS activity.

Adaptation, Physiological↗

Substance P evokes slow and fast responses in cultured myenteric neurons of the guinea pig.

Intracelluar electrical recordings were made from myenteric neurons in tissue culture. Most of the neurons were found to be very sensitive to substance P (SP), which was applied by pressure from micropipettes. SP evoked two different responses: slow depolarizations with latencies of 1-5 s and durations of 1-2 min, and fast depolarizations with latencies of 30-50 ms and durations of 1-10 s. These may represent two distinct response mechanisms to SP.

Animals↗

Physiological and pharmacological studies of the internal anal sphincter in the rat.

The rectoanal reflex in the rat consists of relaxation followed by contraction of the internal anal sphincter (IAS). Beta-adrenergic drugs produce prolonged relaxation of the IAS, where alpha-agonists cause brief relaxation followed by contraction. Muscarinic cholinergic drugs contract the IAS. ATP and related purines produce relaxation which is blocked by theophylline. The reflex persists during adregeneric, cholinergic, and purinergic block. The potassium-blocker apamin prevents the relaxation induced by rectal distension. This suggests that the reflex is not mediated by adrenergic, cholinergic, or purinergic transmitters. Blocking potassium conductance was apparently the only way to eliminate this reflex.

Acetylcholine↗

The enteric nervous system in tissue culture. III. Studies on neuronal survival and the retention of biochemical and morphological differentiation.

The maintenance of differentiated properties and survival rates of enteric neurons, grown in explant cultures for periods of up to 3 weeks, was studied. Using catecholamine fluorescence, immunohistochemistry and autoradiography, it was found that adrenergic neurons, VIP-containing neurons and putative GABAergic neurons, which constitute small subpopulations of guinea pig myenteric neurons in vivo, were all represented in plexus explants after maintenance in culture for 2-3 weeks. The pattern of expression of the transmitter-related enzymes, acetylcholinesterase and monoamine oxidase, paralleled that found in in situ studies. Investigation of neuronal structure by intracellular injection of horseradish peroxidase revealed that the cultured neurons continue to express the wide diversity in gross morphology which characterizes these cells in vivo. Employing autoradiography following uptake of [3H]GABA to label putative GABAergic neurons, their survival rate from days 1 to 15 of culturing was determined. No neuronal death was detected between days 1 and 5, while the number of neurons decreased between days 5 and 15. These observations suggest that enteric neurons maintained in explant cultures survive well and maintain to a high degree their histochemical and morphological properties.

Animals↗

Receptive field properties of horizontal cells in the tiger salamander retina: contributions of rods and cones.

The spatial properties of horizontal cells in the tiger salamander retina were studied with intracellular electrodes. It was found that when the rod input to horizontal cells is dominant the receptive fields are smaller than those measured under conditions of strong cone activation. A possible explanation for this finding is that rod signals undergo greater lateral attenuation within the horizontal cell network.

Action Potentials↗

The contribution of pigment transitions to sensitivity changes in the barnacle photoreceptor and the correlation with the prolonged depolarizing afterpotential.

A conditioning light can cause a decrease (adaptation) or an increase (facilitation) in the sensitivity of barnacle photoreceptors, as measured by the amplitude of the late receptor potential (LRP). We show that a net transfer of visual pigment from the rhodopsin (R) to the metarhodopsin (M) state induces a large facilitation whereas the reverse transfer results in a much smaller facilitation or even an adaptation. These effects were not due to the response to the conditioning light but to the pigment reactions. When the conditioning light did not alter the pigment population (i.e., M leads to M, R leads to R) it was followed by an intermediate degree of facilitation. These conclusions are correct for cells which have relatively low sensitivity. In sensitive cells, all pigment transitions produce adaptation. LRP facilitation and the prolonged depolarizing afterpotential (PDA) show several common characteristics with respect to pigment transitions: 1. Their magnitude increases with the amount of pigment transferred from R to M. 2. Both are depressed by the M leads to R transition. 3. Their production is impeded by the M leads to R transition. 4. The PDA itself is facilitated by the R leads to M transition and this facilitation decays with a time course comparable to that of LRP facilitation. These results suggest that there may be an underlying process common to LRP facilitation and PDA.

Animals↗

Myenteric neurons express electrophysiological and morphological diversity in tissue culture.

Intracellular recordings were taken from neurons of the myenteric plexus of the guinea-pig caecum grown in tissue culture. Subsequently horseradish peroxidase (HRP) was injected into the same neurons for examination by light and electron microscopy. Neurons showed a variety of electrophysiological responses, including S- and AH-cell type behavior, similar to those reported for myenteric neurons in situ, and depolarization to iontophoresis of acetylcholine. Neurons resembling Dogiel type I, type II and intermediate forms, and nerve varicosities which contained small agranular, large granular or large opaque vesicles were observed.

Action Potentials↗

Diamide, a sulfhydryl reagent, modifies the light response of Limulus ventral photoreceptors.

Responses to light were recorded intracellularly from Limulus ventral photoreceptors during the application of diamide, a sulfhydryl oxidizing agent. At diamide concentrations of over 0.5 mM there was a brief phase of increased response followed by a marked decrease. Diamide also prolonged the response latency, and in several cases increased the frequency of spontaneous discrete waves. At concentrations of 0.25 mM and below, the response only increased. Although the underlying mechanisms of these effects are not understood, these findings may be significant for the understanding of transduction in photoreceptors.

Action Potentials↗

Rod and cone signals in the horizontal cells of the tiger salamander retina.

1. Intracellular recordings of horizontal cell responses to monochromatic lights of various wave-lengths and intensities were made in the retina of the larval tiger salamander in order to determine the contributions of rod and cone activities to horizontal cell responses. 2. Under conditions of extensive dark adaptation, and with dim light stimulation, the horizontal cell responses reflected mainly rod activity. In the light-adapted state or at high light intensities the cone contribution was dominant. 3. Bright adapting flashes selectively suppressed the rod component of horizontal cell responses. 4. Intracellular recordings from rods and cones showed that interactions between the two receptor types are very small and cannot account for the large rod--cone mixed input observed in horizontal cells. It is concluded that this input is mediated by direct connexions between receptors and horizontal cells.

Adaptation, Ocular↗

A potassium contribution to the response of the barnacle photoreceptor.

1. Intracellular recording from photoreceptors in the lateral eye of the barnacle show a brief negative-going 'dip' shortly after the onset of the late receptor potential. This phase can sometimes result in a hyperpolarization relative to the resting membrane potential. 2. The dip is prominent in light-adapted cells and is reduced by dark-adaptation. Low extracellular Ca2+ also reduces it. 3. The amplitude of the dip changes inversely with the K+ concentration in the saline. 4. The amplitude of the dip depends on the membrane potential, with a reversal potential near - 80 mV. 5. K+ blocking agents such as quinine and quinidine reduce or abolish the dip. 6. These observations indicate that the dip is due to a brief increase in K+ conductance which may be dependent on an influx of Ca ions. The fast decay of this phase may be brought about by a rapid uptake of Ca2+ by an intracellular mechanism.

Adaptation, Ocular↗

Adaptation and facilitation in the barnacle photoreceptor.

The barnacle photoreceptor sensitivity may either decrease (light adaptation) or increase (facilitation) after exposure to a conditioning light. The balance between adaptation and facilitation is influenced by at least three factors: initial sensitivity state of the cell, external calcium concentration, and conditioning intensity. Cells of very high sensitivity show mainly adaptation, which appears only for higher conditioning intensities and is suppressed in low-calcium media. Less sensitive cells, or those whose sensitivity is reduced by injury or metabolic decay, exhibit facilitation, expecially in low-calcium media and at intermediate conditioning intensities. Both phenomena show recovery time-courses of seconds-to-minutes. Models are proposed which relate light adaptation, as previously suggested, to increased internal calcium concentration, and facilitation either to decreased internal calcium concentration or to decreased activation "affinity" of ion-channel-blocking sites.

Animals↗

Backbone cyclization of the C-terminal part of substance P. Part 1: The important role of the sulphur in position 11.

Novel backbone-to-side chain and backbone-to-backbone cyclic analogues of substance P (SP) were prepared by solid-phase synthesis and screened for biological activity. An analogue containing a thioetherlactam ring between positions 9 and 11 showed an EC50 value of 20 nM toward the neurokinin 1 (NK-1) and was inactive toward the NK-2 and NK-3 receptors. On the other hand, in a multiple backbone cyclic peptide library of similar analogues, in which the sulphur was excluded from the ring, very low activity was detected. The activity was re-evaluated and was found to be even lower (EC50 = 0.11 mM) than the previously published data. These results indicate that the thioether moiety has a crucial role in receptor activation. The results also show tolerance of the NK-1 receptor, but not NK-2 or NK-3, to cyclization of the C-terminal portion of the SP6-11 hexapeptide.

Animals↗

Direct inhibitory effect of erythromycin on the gallbladder muscle.

Erythromycin, a macrolide antibiotic, stimulates motor activity in various parts of the gastrointestinal tract in humans and animals. This effect of erythromycin resembles that of motilin, a gastrointestinal hormone, in evoking contractions similar to phase 3 activity of the migrating motor complex. Motilin induces contractions in the canine gallbladder but fails to evoke any response, either in vivo or in vitro, in the human gallbladder. Surprisingly, erythromycin stimulates human gallbladder emptying in healthy volunteers and in persons with diabetic autonomic neuropathy. In the present study we examined the effect of erythromycin on chemically and electrically evoked contractions of isolated gallbladders from guinea pigs and humans by use of isometric force measurements. Carbachol, a muscarinic cholinergic agonist, evoked gallbladder contractions that were diminished by erythromycin in a concentration-dependent manner: at 200 micromol/L the contractions were 86% +/- 20% of the control response, at 500 micromol/L they were 63% +/- 21% of control, and at 1000 micromol/L they were 41% +/- 20% of control (P <0.05, N = 10, mean +/- standard deviation). Electrically evoked gallbladder contractions were reduced to 68% +/- 18% of the control response with the addition of 500 micromol/L of erythromycin and to 56% +/- 19% of control after the addition of 1000 micromol/L (P <0.05, N = 8). Guinea pig but not human gallbladders contracted after stimulation with the alpha-adrenergic agonist phenylephrine. Erythromycin reduced these contractions in a concentration-dependent manner but had no effect on gallbladder contractions induced by bradykinin. In human gallbladder strips, erythromycin at 500 micromol/L reduced the contractile response to electrical stimulation to 71% +/- 16% of the control value (N = 10 [5 patients], P <0.01) and the carbachol-evoked contractions to 53% +/- 24% (P <0.01, N = 32). The inhibitory effect of erythromycin persisted in the presence of the nerve blocker tetrodotoxin at 1 micromol/L. It is concluded that erythromycin has a direct inhibitory effect on guinea pig and human gallbladder contractions.

Adrenergic alpha-Agonists↗

Liquid enteral diets induce bacterial translocation by increasing cecal flora without changing intestinal motility.

The aim of this study was to determine the contribution of intestinal motility and cecal bacterial overgrowth to liquid diet-induced bacterial translocation (BT). Three different commercially available liquid diets were offered to mice for 1 week. BT to the mesenteric lymph nodes (MLN), spleen, and liver were examined as well as cecal bacterial counts and populations, small bowel length and weight, and histopathologic changes in the ileal and jejunal mucosa. In addition, the effect of the various diets on intestinal motility was measured by the transit index of a charcoal mixture introduced into the stomach. The incidence of BT to the mesenteric lymph nodes was significantly and similarly increased (p < .05) in mice fed Vivonex (30%), Ensure (30%), and Osmolite (33%) compared with chow-fed controls (0%). Compared with chow-fed controls, all three liquid diets were associated with the development of cecal bacterial overgrowth (p < .01). There were no significant changes in the transit index for the three liquid diet groups compared with the chow-fed controls. BT to the MLN was induced by all three liquid diets tested, casting some doubts as to their role in preventing BT in clinical use. BT was associated with a statistically significant increase in cecal bacterial count but was not associated with gut motility changes in this model. In fact, no significant changes in intestinal motility were noted in all groups tested.

Animals↗

Pentazocine reduces cholinergic responses in the guinea-pig extrahepatic biliary tract by a non-opiate mechanism.

The mechanical responses of the guinea-pig gallbladder and common bile duct to pentazocine were measured in vitro. At concentrations of 1 microM or higher, pentazocine reduced the responses of the gallbladder and common bile duct to electrical stimulation and to carbachol. This antagonism was not blocked by naloxone and appears to be due to an atropine-like action of pentazocine. At concentrations of 5 microM or higher pentazocine induced gallbladder contraction which was naloxone-insensitive. Both effects were not affected by tetrodotoxin and appear to be due to direct action on the muscle. The antimuscarinic activity of pentazocine should be taken into consideration when this opioid is administered experimentally or clinically.

Animals↗