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PubMed1977

Nicotine-like effect of prostaglandin F2alpha on longitudinal smooth muscle of cat jejunum.

The effect of hexamethonium (1 x 10(-6) M) chlorpromazine (1 x 10(-6) M) and physostigmine (1 x 10(-7) M) on the spastic effects of PGF2alpha (3 x 10(-7) M), PGE1 (3 x 10(-7) M) acetylcholine (1 x 10(-8) M) and nicotine (1 x 10(-7) M), was studied on isolated longitudinal smooth muscle of cat jejunum. The contractile effects of PGF2alpha and nicotine were found to decrease on an analogous scale as a result of hexamethonium and chlorpromasine administration and to be potentiated by physostigmine. Hexamethonium and chorpromazine do not influence significantly the spastic effects of acetylcholine, physostigmine potentiates them less markedly. Hexamethonium reduces whereas physostigmine and chlorpromazine potentiate the contractile effect of PGE1. Taking into consideration also the results of previous studies (Petkov, Radomirov, 1977), it is assumed that the contractile effect of PGF2chi on the longitudinal muscle of cat jejunum is at least partly mediated through ganglionic stimulation, i.e. the mechanism of the spastic action of PGF2chi on the smooth muscle used has at least partly a nicotine-like character.

Animals↗
PubMed1983

Comparative effects of some autonomic drugs on lizard (Agama agama) and tortoise (Kinixys crosa) isolated rectum.

The effects of some cholinomimetic and sympathomimetic drugs have been investigated on the isolated rectal muscles of West African rainbow lizard (Agama agama) and land tortoise (Kinixys crosa). Acetylcholine and its natural or synthetic analogues evoked concentration-related atropine-sensitive contractions of the muscle preparations, whereas all the catecholamines examined relaxed the lizard (and guinea-pig), but not the tortoise, isolated rectum in a dose-dependent fashion. The ganglionic stimulant drugs used, nicotine and DMPP, did not produce any effect on the isolated rectum of the two reptiles, although they contracted the guinea-pig isolated rectum in a concentration-dependent manner. Concentrations of physostigmine, which induced spasms or contractions in the isolated rectum of the guinea-pig, failed to excite reptilian rectal muscle preparations. Histamine induced biphasic responses in the lizard isolated rectum without affecting the isolated rectum of the tortoise. Serotonin (5-HT) which contracted the isolated rectum of the guinea-pig (like histamine) also provoked variable contractions of the lizard rectum but did not affect the tortoise isolated rectum. It is therefore concluded that although the rectal smooth muscles of these two terrestrial West African reptiles possess cholinergic innervation with mainly "muscarinic" cholinoceptors, their autonomic innervation differs from that of a conventional mammalian (e.g. guinea-pig) gastrointestinal tract smooth muscle.

Acetylcholine↗
PubMed1982

The effects of d-nicotine and l-isomer on nicotinic receptors.

The effects of optically pure d-nicotine were investigated as compared with those of the l-isomer. d-Nicotine showed qualitatively the same effects as the l-isomer in the ganglionic or neuromuscular sites and the relative potency of the d-isomer was approximately 0.06 in the case of rat blood pressure (elevation), approximately 0.2 in the cat superior cervical ganglion (stimulation and blockade) and approximately 1.0 in the neuromuscular junctions of the rat diaphragm (blockade). In the adrenergic nerve terminals of the isolated rabbit pulmonary artery, l-nicotine produced sympathomimetic effects by releasing norepinephrine from those terminals. d-Nicotine, on the other hand, did not produce such effects, but instead inhibited those effects due to the l-isomer. Because d-nicotine had no effect on the response to exogenously applied norepinephrine and blocked the 3H-efflux induced by the l-isomer from the preparations preincubated with [3H]norepinephrine, the inhibitory effect of the d-isomer was attributed to its presynaptic action. Such an inhibitory effect of d-isomer was noncompetitive, on the basis of the shift of the concentration-contraction curve with the l-isomer. Simultaneous application of both isomers produced no inhibition of the response to the l-isomer, irrespective of the concentration of d-nicotine. Occurrence of the inhibitory effect of d-nicotine was not prevented by hexamethonium. d-Nicotine did not inhibit the responses of the artery to electrical transmural stimulation. These results indicate that d-nicotine inhibits the response to l-isomer by acting neither on the nicotinic receptors nor on excitation-secretion coupling mechanisms. Furthermore, such an effect of the d-isomer would be similar to that reported in the case of l-isomer, i.e., "nicotinic desensitization."

Animals↗
PubMedDate not supplied

The dual role of serotonin in leech swimming.

The swimming behavior of the leech depends upon the level of serotonin in its blood stream: the higher the level, the more likely the leech is to swim. Serotonin is contained in Retzius cells, segmentally paired neurons, which release enough of this substance to affect its blood level and thus the swimming behavior of the animal. Retzius cells appear not to have synaptic effects on swim-related neurons. Pairs of other serotonin-containing neurons (cells 21 and 61) are also present in each ganglion. Stimulation of these cells can initiate swimming within seconds. In contrast to Retzius cells, neurons 21 and 61 make synaptic connections onto swim-related neurons; for example, cell 61 makes what appears to be a conductance decrease excitatory synapse onto the pattern-generating interneuron cell 208. These results suggest that the two classes of serotonin-containing neurons control the swimming behavior of the leech through two different mechanisms: Retzius cells exert a neurohormonal action whereas cells 21 and 61 act synaptically.

Animals↗
PubMed1980

Toxicity and drug interactions of levamisole.

Clinical signs and lesions of levamisole toxicosis include: nausea, vomiting, increased salivation, frequent urination and defecation, colic, dizziness, headache, muscle tremors, ataxia, anxiety, hyperesthesia with irritability, clonic convulsions, depression, rapid respiration, dyspnea, prostration, collapse, hemorrhages in the subepicardium and thalamus, enteritis, hepatic degeneration and necrosis, and splenic congestion. Most of these signs and lesions are similar to those observed in nicotine poisoning. Levamisole causes vasopressor and panting effects which are blocked by ganglionic blocking agents hexamethonium and mecamylamine but are not blocked by atropine. The vasopressor effect of levamisole is blocked by alpha-adrenergic antagonists phentolamine and dibenamine; however, the respiratory effect of levamisole is not affected by these alpha-adrenergic antagonists. Repeated IV injections of levamisole cause a tachyphylactic response. With levamisole-induced tachyphylaxis, the effects of other ganglionic stimulants dimethylpiperazinium and nicotine are also abolished. Levamisole causes an electroencephalographic arousal which is antagonized by atropine sulfate and mecamylamine. There is also a structural similarity of levamisole to nicotine. These studies suggest that levamisole is a nicotine-like compound. Possible treatment of levamisole poisoning is discussed. Drug interactions of levamisole with organophosphates and anthelmintics, eg, pyrantel, methyridine, and diethylcarbamazine, are also discussed.

Animals↗
PubMed1980

Mechanism of the antihypertensive action of clonidine on the pressor response to physostigmine.

Physostigmine (P) was used as a model in anesthetized rats for the development of hypertension by a central cholinergic mechanism. P (25-100 micrograms/kg i.v.) produced a dose-related increase in mean arterial pressure which was inhibited 30 to 90% by preinjection of clonidine (100 micrograms/kg i.v.). This dose of clonidine was without effect on the pressor response to ganglionic stimulation produced by 1,1-dimethyl-4-phenylpipera-zinium iodine. To examine further the central inhibitory effect of clonidine on the pressor response to P, regional brain acetylcholine turnover rate was measured in control and clonidine-pretreated rats. Clonidine significantly reduced turnover in hypothalamus (69%), pons-medulla (43%) and midbrain (39%) but not in striatum or hippocampus. These observations are consistent with an inhibitory effect of clonidine on central cholinergic neurons involved in cardiovascular regulation.

Acetylcholine↗
PubMedDate not supplied

Androgenic regulation of NO availability in rat penile erection.

Prior studies from this laboratory, using untreated castrated (CASTRATE) rats and testosterone-treated castrated (TESTO) rats, have shown that the magnitude of the intracavernosal pressure increase during erection is androgen dependent. Studies from this and other laboratories have also presented evidence suggesting that penile erection is mediated principally by nitric oxide (NO). The present report was designed to confirm that androgens maintain the availability of cavernosal NO and to determine if this androgenic action is exerted at the genomic level modulating the expression of the neuronal form of the nitric oxide synthase gene (nNOS). The results showed that administration of supplemental L-arginine failed to augment the erectile response in either group, suggesting that substrate availability is not a cause of the reduced response in CASTRATE animals. Inhibition of NO synthesis with a nitro-arginine competitive inhibitor of nitric oxide synthase enzyme protein (NOS) resulted in strong inhibition of erection in both TESTO and CASTRATE rats. When given in conjunction with ganglionic stimulation to induce erection, the NO releasing drug, sodium nitro-prusside (SNP), increased intracavernosal pressure in CASTRATE rats but not in TESTO rats, suggesting a deficiency of the available NO in CASTRATE-animals. Finally, reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that mRNA levels for the enzyme nNOS in the penis were greater in TESTO animals than in CASTRATE rats. These results support the hypothesis that androgens mediate the erectile response in the rat penis by stimulating the expression of the neuronal isoform of nitric oxide synthase, thus maintaining an adequate supply of NO.

Analysis of Variance↗
PubMed1998

Discrimination between monomorphic and polymorphic ventricular tachycardia using cycle length variability measured by wavelet transform analysis.

The objective of this study was to assess the capability of wavelet transform (WT) analysis to differentiate between monomorphic (MVTs) and polymorphic ventricular tachycardias (PVTs) in a canine model and to relate these results to epicardial isochronal maps on a beat-by-beat basis. Unipolar electrograms were simultaneously recorded from the surface of both ventricles with a 127-lead sock electrode array in 24 open-chest anesthetized dogs. The sampling frequency was 500 Hz. Atrioventricular block was induced by formaldehyde injection into the atrioventricular node. The left anterior descending coronary artery was occluded for 60 minutes under ventricular pacing (140 stimuli/min) followed by reperfusion. Ventricular tachycardias were obtained during reperfusion and during left stellate ganglion stimulation. After visual selection, a total of 97 segments of 2,048 samples (4.096 seconds) were extracted and classified as 67 MVTs and 30 PVTs. A parameter based on the cycle length variability was defined in the second scale of the WT decomposition, normalized by its mean value. Similar assessment of cycle length variability was performed based on the detection of the point of most rapid change in potential with a negative slope in excess of -0.5 mV/ms in each individual electrogram to test the accuracy of the results obtained with the WT parameter. The WT parameter correctly identified 97% MVT and 83.3% PVT segments, for an overall accuracy of 92.8%. Beat-by-beat epicardial maps of MVT displayed a cluster of sites of initial activation close to the reperfusion area, while the sites of breakthrough from beats during PVT were much more dispersed over both ventricles. A strong and significant correlation was found between the number of electrodes with the earliest epicardial activation and the WT parameter (r = .78, P < .0001). To test the accuracy of the results obtained, a comparison was performed between the WT parameter (0.082 +/- 0.007) and the cycle length variability, estimated as the normalized standard deviation of the intervals between individual electrograms (0.076 +/- 0.006). No significant differences were shown (P = .0022), and a strong linear correlation was found between both measurements (Pearson correlation coefficient, .966). It is concluded that WT analysis discriminated accurately between MVT and PVT, and a quantitative relation was found with the spatial dispersion of sites of earliest epicardial activation. The WT results strongly correlated with those obtained by another method of estimating cycle length variability. Methodologically, the strength of the WT lies in the complementary information that could be extracted from the processing of electrograms to enhance the detection/discrimination of different types of arrhythmias.

Animals↗
PubMed1999

Induction of eclampticlike changes by stimulation of the celiac ganglion in rats.

OBJECTIVE: To examine the relation between the stimulation of the abdominal sympathetic nervous system and vasospasm of the brain in eclamptic seizures, we analyzed brain blood flow after stimulation of the celiac ganglion by lipopolysaccharide (LPS, 5, 50, or 500 mg/mL) or normal saline before and after denovation of sympathetic trunk in pregnant and nonpregnant rats. METHODS: The brain blood flow was measured after stimulation of the celiac ganglion with 50 microL (5 mg/mL) LPS in group I, 50 microL (50 mg/mL) LPS in group II, 50 microL saline in group III, and 50 microL (500 mg/mL) LPS (after denovation of the sympathetic trunk) in group IV. A sham control experiment was also done by stimulation of the abdominal peritoneum with 50 microL (500 mg/mL) LPS in group V. Changes in water content and histological findings in the brain were also studied in this protocol. RESULTS: A significant reduction in brain blood flow was observed in pregnant rats in groups I and II on stimulation of the celiac ganglion with LPS (p < 0.0001, p < 0.001) compared with before stimulation. Celiac ganglion stimulation with saline (group III) and LPS (group IV, after denovation of the sympathetic trunk) did not affect brain blood flow. Stimulation of the abdominal peritoneum with LPS (group V) could not induce any changes in brain blood flow. Repeated seizures occurred in 60% of pregnant rats and a remarkable increase in water content was observed after LPS stimulation of the celiac ganglion in groups I and II (p < 0.0001, p < 0.001). Histologically, we found that stimulation of the celiac ganglion with LPS caused widening of perivascular spaces with compression of the vessels leading to ischemic changes in brain tissues. There were no such findings observed in other groups. However, a lesser extent effect was noticed in nonpregnant than seen in pregnant rats. CONCLUSION: Stimulation of the abdominal sympathetic ganglions could induce vasoconstriction of the brain vessels, thus decreasing brain blood flow, which results in eclampsialike changes in rats.

Animals↗
PubMed1994

Evaluation of patients with atypical trigeminal neuralgia for permanent electrode implant by test stimulation of the ganglion gasseri.

The treatment of so-called atypical trigeminal neuralgia, characterized by long-lasting burning pain sensations without any pain attacks was for a long time an unsolved problem in contrast to the so-called 'tic douloreux'. Following the experience with our own patients and other groups, destructive procedures in atypical trigeminal neuralgia frequently result in worsening of the clinical conditions. We have therefore transferred the well-established method in the periphery of therapeutic electrostimulation to the trigeminal region. The evaluation of the patients with atypical trigeminal neuralgia is the key for good therapeutic results. Therefore percutaneous test stimulation of the ganglion gasseri has to be performed during a hospital stay. 54% of 149 patients experienced pain relief during test stimulation. Therefore in 81 patients with positive test results, electrodes were implanted together with a neurological pulse generator (Itrel Medtronic).

Electric Stimulation Therapy↗
PubMed1994

Calcium concentration changes in the calyciform nerve terminal of the avian ciliary ganglion after tetanic stimulation.

A study has been made of the changes in calcium concentration in the calyciform nerve terminal ([Ca]c) and in the neurone soma ([Ca]s) of avian ciliary ganglion cells following tetanic stimulation of the nerve terminal. Dissociated ciliary neurones were loaded with the calcium indicator Fura-2 and digital imaging techniques used to determine the spatial and temporal distribution of calcium in the cells during post-tetanic potentiation (PTP) and long-term potentiation (LTP). Stimulation of the calyciform terminal with an extracellular electrode at 10 Hz for 2 s increased both [Ca]s and [Ca]s over 3-fold, with the [Ca] increasing for each impulse in the facilitatory train. The increase in [Ca]s could be prevented by allowing the terminal to degenerate in culture before stimulation. Stimulation of the calyciform terminal with a long tetanus of 30 Hz for 20 s gave an over 4-fold increase in both [Ca]c and [Ca]s by the end of the train. Analysis of the decline in [Ca]c after the train showed that it disappeared from the calyx along a double exponential time course with time constants of about 1 min and 50 min, respectively. These times are similar to those of PTP and LTP in the ganglia, and are almost independent of the extracellular calcium level. In order to determine whether the influx of calcium ions during a tetanus was through N-type calcium channels, these were blocked with adenosine (100 microM). Adenosine blocked the increase in both [Ca]s and [Ca]c that normally accompanies a tetanus. Thapsigargin (200 nM) did not affect [Ca]c or [Ca]s, but blocked transient increases in [Ca] caused by caffeine (10 mM) in both 3 mM and Ca2+ free bath solutions. These results are discussed in relation to the role of intracellular calcium in initiating LTP after a tetanus to the nerve terminals.

Adenosine↗
PubMed1975

[Structure of the neurons of the spiral and vestibular ganglia and changes in them under conditions of adequate stimulation].

The ganglionic cells of the eighth nerve ganglia were studied. The cells of the vestibular and spiral ganglion were similar in structure. Changes in the ultrastructure involving the mitochondrial apparatus, and squamous endoplasmic reticulum and the nucleus took place in the ganglionic cells under effects of stimulation (sound, angular accelerations, vibration). These shifts appear to be morphological manifestations of the ganglionic cell metabolism under the influence of a specific stimulus.

Acoustic Stimulation↗
PubMed2000

alpha-eudesmol, a P/Q-type Ca(2+) channel blocker, inhibits neurogenic vasodilation and extravasation following electrical stimulation of trigeminal ganglion.

In this study, we investigated the effect of alpha-eudesmol, which potently inhibits the presynaptic omega-agatoxin IVA-sensitive (P/Q-type) Ca(2+) channel, on neurogenic inflammation following electrical stimulation of rat trigeminal ganglion. Treatment with alpha-eudesmol (0.1-1 mg/kg. i.v.) dose-dependently attenuated neurogenic vasodilation in facial skin monitored by a laser Doppler flowmetry. In addition, alpha-eudesmol (1 mg/kg. i.v.) significantly decreased dural plasma extravasation in analysis using Evans blue as a plasma marker. On the other hand, alpha-eudesmol (1 mg/kg, i.v.) did not affect mean arterial blood pressure in rats. The calcitonin gene-related peptide (CGRP) and substance P (SP) released from activated sensory nerves have recently been suggested to be associated with the neurogenic inflammation. In this study, we also showed that alpha-eudesmol (0.45-45 microM) concentration-dependently inhibits the depolarization-evoked CGRP and SP release from sensory nerve terminals in spinal cord slices. These results indicate that the anti-neurogenic inflammation action of alpha-eudesmol, which does not affect the cardiovascular system, may be due to its presynaptic inhibition of the neuropeptide release from perivascular trigeminal terminals. We also suggest that the omega-agatoxin IVA-sensitive Ca(2+) channel blocker, alpha-eudesmol, may become useful for the treatment of the neurogenic inflammation in the trigemino-vascular system such as migraine.

Animals↗
PubMed2006

Electrical stimulation of mammalian retinal ganglion cells with multielectrode arrays.

Existing epiretinal implants for the blind are designed to electrically stimulate large groups of surviving retinal neurons using a small number of electrodes with diameters of several hundred micrometers. To increase the spatial resolution of artificial sight, electrodes much smaller than those currently in use are desirable. In this study, we stimulated and recorded ganglion cells in isolated pieces of rat, guinea pig, and monkey retina. We used microfabricated hexagonal arrays of 61 platinum disk electrodes with diameters between 6 and 25 microm, spaced 60 microm apart. Charge-balanced current pulses evoked one or two spikes at latencies as short as 0.2 ms, and typically only one or a few recorded ganglion cells were stimulated. Application of several synaptic blockers did not abolish the evoked responses, implying direct activation of ganglion cells. Threshold charge densities were typically <0.1 mC/cm2 for a pulse duration of 100 micros, corresponding to charge thresholds of <100 pC. Stimulation remained effective after several hours and at high frequencies. To show that closely spaced electrodes can elicit independent ganglion cell responses, we used the multielectrode array to stimulate several nearby ganglion cells simultaneously. From these data, we conclude that electrical stimulation of mammalian retina with small-diameter electrode arrays is achievable and can provide high temporal and spatial precision at low charge densities. We review previous epiretinal stimulation studies and discuss our results in the context of 32 other publications, comparing threshold parameters and safety limits.

Action Potentials↗
PubMed1974

Concomitant changes in formaldehyde-induced fluorescence of dopamine interneurones and in slow inhibitory post-synaptic potentials of the rabbit superior cervical ganglion, induced by stimulation of the preganglionic nerve or by a muscarinic agent.

1. Dopamine was identified by formaldehyde histochemistry and cytospectrofluorometry in the rabbit's superior cervical ganglion. Dopamine was localized to the intraganglionic ;small intensely fluorescent' cells, and also to the characteristically beaded fibres forming a network in close contact with virtually all ganglion cell bodies. The extensive beaded fibres are therefore presumed to be processes of the small intensely fluorescent cells.2. Changes in the dopamine content of these interneurones were studied by recording alterations in their relative fluorescence intensity in conjunction with changes in the slow inhibitory post-synaptic potential (s.-i.p.s.p.) response of the ganglion to orthodromic nerve input.3. Dopamine content was lower after several hours in vitro even without special stimulation; this was in accord with a regularly observed spontaneous reduction of the s.-i.p.s.p. response.4. After a period of conditioning stimulation of the preganglionic nerve, in the presence of an anticholinesterase agent (eserine) and an inhibitor of catecholamine synthesis (alpha-methyl-p-tyrosine), the s.-i.p.s.p. was selectively and markedly reduced. The dopamine fluorescence in the small intensely fluorescent cell interneurones was also significantly reduced, to a mean value of about 55 or 60% of the fluorescence in the dopamine interneurones of the paired but unstimulated control ganglion. A significant reduction in dopamine fluorescence was always accompanied by a marked loss of s.-i.p.s.p. response; the reverse was not always true.5. Treatment with the muscarinic agent bethanechol for 30 min, with no alpha-methyl-p-tyrosine or eserine present, similarly resulted in reductions in the s.-i.p.s.p. response of the ganglia and in the formaldehyde-induced fluorescence of the dopamine interneurones.6. A functional uptake of extrinsic dopamine by the dopamine interneurones was also demonstrated: temporary exposure to dopamine restored a large fraction of both the s.-i.p.s.p. response and the dopamine fluorescence of the small intensely fluorescent cells, in ganglia already subjected either to the conditioning stimulation of the preganglionic nerve or to the action of bethanechol.7. It is concluded that (a) preganglionic impulses, by a cholinergic muscarinic synaptic action, can induce a release of dopamine from dopamine interneurones (small intensely fluorescent cells) in the superior cervical ganglion, (b) the ability of the ganglion to respond with a s.-i.p.s.p. to orthodromic input may be viewed as being dependent on the supply of functionally releasable dopamine in these interneurones, (c) the functionally releasable transmitter in vitro appears to comprise roughly 50% of the total dopamine content of the interneurones, and (d) the results fulfil some of the requirements of the hypothesis that a dopamine interneurone is activated muscarinically by preganglionic nerve impulses and mediates the production of s.-i.p.s.p. in sympathetic ganglion cells.

Action Potentials↗
PubMed1987

Reflex responses of neurons in the inferior mesenteric ganglion to mechanical stimulation of the colon, rectum, anal canal, and urinary bladder in the dog.

Unitary discharges were recorded from the inferior mesenteric ganglion of decerebrate dogs. Eighty-one units were identified as sympathetic postganglionic neurons innervating the colon and rectum by collision test performed by stimulation of the lumbar colonic nerve. Discharges of four units were enhanced simultaneously with an increased outflow of the renal nerve by pinching a toe. Thus, those units were regarded as vasoconstrictors of colonic blood vessels. Sixty-five units whose discharges were depressed or not affected by the pinching were regarded as neurons innervating colonic smooth muscle or mucosa (colonic units). Discharges were enhanced in the majority of the colonic units by colonic, rectal, and vesical distension, and mechanical stimulation of the anal canal, while discharges were depressed in a few units by rectal and vesical distension, and the anal canal stimulation. The number and percentage of the depressed units increased not only after cutting the hypogastric nerves and descending branches of the lumbar colonic nerve but also after transection of the caudal pons. The reflex depressions disappeared after transection at the bulbospinal junction, but the reflex enhancements remained. These results indicate that the colonic units are enhanced through a spinal reflex by the inflows from the distal colon, rectum, anal canal, and urinary bladder through the lumbar colonic, hypogastric, pelvic, and pudendal nerves, while a few are inhibited through a supraspinal reflex by inflows through the pelvic and pudendal nerves.

Action Potentials↗