Mast cell mediators excite the afferents of cat small intestine.

The influence of intra-arterial injections of 5-hydroxytryptamine, histamine and prostaglandin E2 on afferent impulse activity of mesenteric nerves of small intestine was studied. In anaesthetized cats 5-hydroxytryptamine (10(-5)-10(-4) M) and histamine (10(-5)-10(-3) M) were shown to increase the impulse activity in a dose-dependent manner. Metergolin, 5-hydroxytryptamine antagonist, suppressed the effect of 5-hydroxytryptamine. Clemastine and cimetidine, antagonists of H1 and H2 histamine receptors respectively, distinctly diminished excitatory histamine effects. Prostaglandin E2 (10-30 micrograms/kg) enhanced the afferent impulse activity. The results suggest that afferents of the small intestine may be involved in reception of inflammatory and immune responses.

Reception of low-intensity millimeter-wave electromagnetic radiation by the electroreceptors in skates.

Low intensity millimeter-wave electromagnetic radiation of less than 10 mW cm-2 power intensity has a nonthermal effect on the body and it is widely used in medical practice for treatment of various diseases. Nevertheless, the effect of EMR on biological tissues is not understood. The skin and its sensory receptors are considered to be responsible for EMR reception, but this has yet to be confirmed. The present experiments were designed to study the effect of millimeter-wave electromagnetic radiation on the ampullae of Lorenzini in skates, which are very sensitive to weak electrical stimuli at low frequency. Reception of low-intensity millimeter-wave electromagnetic radiation at 37-55 GHz by the electroreceptors (ampullae of Lorenzini) in the skate has been shown. At a power intensity of 1-5 mW cm-2 irradiating the duct opening at 1-20 mm distance caused a transient increase in the firing rate of a single afferent unit. When the power intensity was increased inhibitory responses were also observed. Some receptors responded with a prolonged excitatory activity lasting up to 30 min to the irradiation of the duct opening. Direct irradiation of the sensory cells produced only an inhibition, probably due to a rise in temperature. It is proposed that millimeter-wave electromagnetic radiation generates a d.c. potential at the vicinity of duct opening which can be detected by the electroreceptors.

Activity of foot skin mechanoreceptors and afferent nerve fibres in the adult rat sciatic nerve are altered after central axotomy of sensory neurons.

The functional properties of skin mechanoreceptors were examined in the hind foot of normal rats in comparison with animals subjected to dorsal rhizotomy. Evoked nerve impulses were recorded from afferent nerve fibres of the tibial nerve. The decentralized mechanoreceptors displayed evidence of autonomous functioning, but with several abnormalities as compared to normal animals. There was a decreased sensitivity to mechanical stimulation and a lower adaptive capacity as a consequence of rhizotomy. The underlying mechanism is suggested to be a loss of central trophic support because of the interrupted link between the central nervous system and the sensory ganglion cell periphery. The findings indicate that mechanical receptors continue functioning under conditions when sensory impulses flow cannot reach postsynaptic target neurons in the central nervous system, but stop at the level of the primary sensory neuron.

Changes in afferent impulse activity of small intestine mesenteric nerves in response to antigen challenge.

Sprague-Dawley rats (weight 130-150 g) were sensitized by an intraperitoneal injection of 1 mg chicken egg albumin with 0.25 ml Freund's adjuvant to stimulate immunoglobulin E antibody production. Leukocyte migration inhibitory factor was used as an indicator of animal sensitization. In acute electrophysiological experiments on sensitized animals, an intra-arterial or intraluminal chicken egg albumin (100 microg) challenge evoked a 10% enhancement of the activity of mesenteric nerves of the small intestine, regardless of the injection site chosen. Afferent nerve activity in control animals was not changed during the chicken egg albumin challenge. Morphometry at the light microscope level showed activation of mast cell degranulation after the antigen challenge to presensitized rats. Intraluminal injections of a stimulator of mast cell degranulation, compound 48/80 (20-30 mg), were found to increase afferent discharges in intact rats. An antagonist of H1 histamine receptors, clemastine, reduced the effect of compound 48/80. The results obtained provide direct evidence for the stimulation of sensory nerve endings by mast cell mediators released during mast cell degranulation.

Epileptiform activity increases the level of nerve growth factor in cerebrospinal fluid of epileptic patients and in hippocampal neurons in tissue culture.

A neurite-stimulating effect was induced by both the cerebrospinal fluid of epileptic patients and the media of co-cultures of rat hippocampus and chick embryo sensory neurons after veratridine treatment. Cerebrospinal fluid from patients with epilepsy stimulated extensive neurite growth in the organotypic culture of chick embryo dorsal root ganglia. The anti-nerve growth factor antibody partly blocked the neurite-stimulating effect of the cerebrospinal fluid. Co-cultures of newborn rat hippocampus and chick embryo dorsal root ganglia were used to investigate the involvement of neurotrophic factors into the processes which are activated by neuronal activity. The data obtained suggest that veratridine, an epileptiform agent, gave rise to an elevation in the level of neurotrophic factors in the culture media and neurite outgrowth of dorsal root ganglia sensory neurons. The anti-nerve growth factor antibody was shown to block the neurite-stimulating effect mediated by veratridine. These results indicate that the epileptiform activity of neurons evokes the expression of neurotrophins.

NMDA receptors in frog semicircular canals.

The effects of competitive (2-amino-5-phosphonovaleric acid) and noncompetitive (Mg2+, ketamine and kynurenic acid) NMDA receptor antagonists were tested in isolated semicircular canals of the frog. All these antagonists reduced the resting firing rate recorded from the whole ampullar nerve of the posterior canal. This suggests that NMDA receptors are present at the cytoneural junctions between hair cells and afferent nerve terminals in frog vestibular organs.

Analysis of L-[3H]-glutamate radioligand binding to plasma membranes of the ampullae of Lorenzini of skates.

Radioligand binding analysis of L-[3H]-glutamate to plasma membranes of the ampullae of Lorenzini in the skate revealed one type of binding site with KD = 286 nM and Bmax = 2.1 pmol mg-1 protein. It was revealed that Na+, K+, Ca2+ and Mg2+ inhibited the L-[3H]-glutamate binding, while Cl- had no effect. The glutamate agonists kainate, quisqualate and N-methyl-D-aspartate (NMDA) were shown to inhibit glutamate binding in a dose-dependent manner. The results obtained confirm the electrophysiological observations suggesting the existence of three types of glutamate receptor at afferent synapses of the ampullae of Lorenzini of skates.

L-serine-O-phosphate blocks NMDA-evoked responses in the ampullae of Lorenzini of skates.

In the present study, we have shown by single afferent unit recording in the organs of Lorenzini that L-serine-O-phosphate (L-SOP) decreases the resting discharge frequency as well as electrically evoked responses. L-SOP in a concentration of 0.1-100 microM antagonizes responses induced by L-glutamate (L-GLU) and N-methyl-D-aspartate (NMDA) and has no effect on the responses to application of kainate (KA) and quisqualate (Q). The results obtained confirm previous observations about the existence of NMDA receptors in the afferent synapse of the ampullae of Lorenzini.

The cerebrospinal fluid from patients with prolactinoma promotes neurite growth of sensory neurones.

The cerebrospinal fluid (CSF) of patients with hypophysis adenomas was used to investigate its effect on organotypic cultures of dorsal root ganglia (DRG) of 10-11 day old chick embryo. Only the CSF from patients with prolactinoma showed a neurite-stimulating effect compared with other hypophysis adenomas.

Brain neurite-stimulating protein promotes formation of mechanosensory endings in sensory neuron.

In the present study we have shown that in the organotypic culture of dorsal root ganglia (DRG) of 10-11 day-old chick embryos, the neurite-stimulating protein (NSP) from bovine brain promotes the development of branching mechanosensory endings. The light and electron microscopic observation revealed that the morphological features of these sensory endings are similar to those in vivo. A mechanical stimulation of these endings elicited bursts of impulses in the sensory neurons.

Actions of dalargin upon single unit activity in the ampullae of Lorenzini of the skate Raja clavata.

In the present study we have shown by single afferent unit recording in electroreceptors of skates (the ampullae of Lorenzini) that the synthetic analogue of leu-enkephalin, dalargin (DAL) at concentrations between 10(-6)-10(-10) M cause a concentration-dependent decrease in the resting discharge frequency as well as a decrease in stimulus evoked responses. The specific opiate antagonist naloxone (NAL, 10(-6) M) antagonizes responses induced by DAL. DAL depresses the excitatory action of L-glutamate (L-GLU). The data obtained speak in favour of the presence of opiate receptors at the synaptic membrane of the ampullae of Lorenzini.

The effect of Mg2+ and Ca2+ on the excitability of Pacinian corpuscles.

The effect of altering extracellular Ca2+ and Mg2+ levels on electrical properties of Pacinian corpuscles of adult cat has been examined. High Mg2+ solution (5--15 mM) increased the excitability of the receptors and the amplitude of the receptor potential. Ca2+-free EDTA solution caused an increase in the amplitude of the receptor potential in the first 60 min and then its decrease. Mg2+ ions slow down or prevent the depressant effect of the Ca2+ lack on the receptor potential. The phase of the receptor potential amplitude increase in Ca2+-free media was reversibly blocked by tetraethylammonium ions. Treatment with 2,4-dinitrophenol produced a transient increase in the receptor potential amplitude. The threshold of the mechanosensitive receptor membrane was unaffected in Ca2+-free or Mg2+-rich solution. The results suggest that divalent cations are not directly involved in the process of mechanoelectric transformation in Pacinian corpuscles.

Physiological properties of lateral line receptors of the lamprey.

Single unit recording from the lateral line nerve of the lamprey revealed the existence of two types of afferents. One type reacts to electric fields (threshold 10-30 microV/cm) and is insensitive to weak mechanical stimuli. The other type is very sensitive to water displacement and does not respond to weak electric fields. The properties of the electroreceptors of the lamprey are discussed and compared with other types of electroreceptors.

Effects of potassium ions on the impulse activity of the ampullae of Lorenzini of the skate.

Perfusion of the basal membrane of the ampullae of Lorenzini with high potassium solution caused a substantial increase in the resting firing rate. This effect was not accompanied by any change in the threshold of the afferent fibres. The low potassium solution caused a decrease in the resting firing rate. When synaptic transmission was abolished by high Mg2+ solution, succeeding perfusion with 10 mM K+ did not induce responses in the afferent fibres. The role of potassium ions in the activity of the ampullae of Lorenzini is discussed.

L-glutamate as possible neurotransmitter in the ampullae of Lorenzini of the skate.

Effects of Mg2+, L-glutamate (L-Glu) and L-glutamic acid diethylester (GDEE) on resting and evoked activities of the ampullae of Lorenzini were studied in marine skates (Raja clavata). Perfusion of the basal membrane with 10(-4)-10(-5) M L-Glu produced significant and reversible changes in resting firing rate depending on initial resting rate. When synaptic transmission was blocked by perfusion with elevated Mg2+, the resting activity was restored if L-Glu (10(-4)-10(-5) M) was added. GDEE (10(-3)-10(-4) M) blocked the synaptic transmission. The results are consistent with the view that L-Glu is the synaptic transmitter in the ampullae of Lorenzini of the skate.

Changes in sensitivities of amplitude and frequency curves of the Hodgkin-Huxley system produced by variations of maximal conductances.

The question of sensitivity of amplitude and frequency curves of the Hodgkin-Huxley system to variations of maximal values of sodium (gNa) and potassium (gK) conductances is considered. Changes in the sensitivity produced by simultaneous changes in gNa and gK values are examined. It has been shown that simultaneous increase of the values of gNa and gK is accompanied by decrease of the sensitivity and, therefore, by improvement of quality of nerve fiber functioning.

Role of neurotrophic factors in adaptational processes of the nervous system.

Neurotrophic factors (NTF) are low-molecular-weight proteins which epigenetically determine neuron survival during embryogenesis and the maintenance of their morphofunctional properties in the adult organism. NTF are located in mesenchymal tissues and reach neuron bodies by means of retrograde axoplasmic transport in nerve fibers; in cell bodies, NTF increase anabolic activity, neurotransmitter synthesis, and structural protein production. Neuron cell bodies have two types of specialized receptors for binding the most common NTF, nerve growth factor (NGF). In the brain, NGF does not affect adrenergic neurons, as it does in the periphery, but acts on cholinergic neurons in the basal part of the forebrain. The forebrain plays the major role in the processes of learning, memory, and plasticity, i.e., in the entire complex of adaptational responses of the nervous system, and these may thus depend on the biological activities of substances, including NTF, in forebrain tissues. An experimental model was developed consisting of organotypic co-cultivation of rat hippocampus fragments with chick embryo dorsal root ganglia. This model was used to demonstrate that epileptiform activity in the hippocampus is associated with increases in NTF release, which can be regarded as an adaptive compensatory response to nerve cell damage occurring during convulsive activity.

Effect of veratridine on the release of neurotrophic factors in nerve tissue cultures.

The depolarizing agent veratridine was shown to affect the level of neurotrophic substances in combined cultures of neonatal rat hippocampus and chick embryo spinal ganglia. In this experimental model, the level of neurotrophic factors in rat hippocampus explants increased as a result of increases in neuronal activity mediated by veratridine. The effects of these neurotrophins on neurite growth in the sensitive spinal ganglion neurons in the combined cultures were evaluated using morphometric methods. Neurite-stimulating effects were seen when veratridine was added to the nutritive medium at a concentration of 90 nM. Antibody to nerve growth factor blocked the action of veratridine. These results demonstrate a role for neuron activity as a regulatory mechanism controlling the expression of neurotrophins.

Effect of low-intensity millimeter-range electromagnetic irradiation on the recovery of function in lesioned sciatic nerves in rats.

The effects of electromagnetic irradiation (EMI) of wavelength 5.6 mm (frequency 53.57 GHz) and power density 4 mW/cm2 on the recovery of function in damaged rat sciatic nerve were studied; damage was produced by nerve section followed by microsuturing. Irradiation was applied to the skin of the thigh in the area of suturing. Total action potential (TAP) recording from the nerve was used to study the functional properties of regenerating nerve fibers five months after lesioning. These experiments demonstrated that EMI had a stimulatory effect on regenerative processes in the nerve, in terms of 25-30% increases in the rate of action potential conduction along nerve fibers, with increases in TAP amplitude.

[The neurite growth stimulating effect of terrilytin on sensory neurons and the spinal cord in tissue culture]. / Stimuliruiushchee rost neiritov deistvie terrilitina na chuvstvitel'nye neirony i spinnoi mazg v kul'ture tkani.

Terrilytin (a protease) was found to promote neurite extension in chick embryo dorsal root ganglia and spinal cord in vitro. This protease was active at the concentration 10-50 ng/ml, which provided extensive neurite outgrowth in the bioassay, compared to the control. Terrilytin may be used for stimulating regenerating processes in nervous tissue.