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Biomedical subjects

M Costa

Publications and source records attributed to M Costa.

At least 415 records · Page 23Linked to original sources
PubMed1987

Effects of nickel(II) on nuclear protein binding to DNA in intact mammalian cells.

An intracellular effect of nickel(II) which may be involved in its carcinogenic action is the alteration of normal DNA-protein binding. This effect of ionic nickel was studied in Chinese hamster ovary cells using several chromatin isolation methods in combination with SDS-polyacrylamide gel electrophoresis. DNA from cells incubated with (35S)-methionine or (35S)-cysteine to radiolabel protein was prepared by three methods: (solation of nuclei or nucleoids followed by chloroform-isoamyl alcohol (24:1 v/v) extraction and in some cases an additional extraction in the absence or presence of 2M NaCl, 40 mM EDTA or SDS; by isopycnic centrifugation through Cs2SO4 gradients containing 0.8% sarkosyl, 2.2 MCs2SO4, 1 mM NaCl and 10 mM EDTA; or by chromatin disaggregation and denaturation using 9 M urea, 2% 2-mercaptoethanol, 4% Nonidet P-40 +/- 2 M NaCl. DNA from nickel-treated cells consistently had more (35S)-methionine radioactivity associated with it than did DNA from untreated cells. This radioactivity was resistant to ribonuclease but sensitive to protease. Differential extraction using denaturing agents and high ionic strength followed by SDS-polyacrylamide gel electrophoresis revealed that most of the tightly bound proteins were nonhistone chromosomal proteins, and possibly histone 1. The enhancement of DNA-protein binding from nickel-treated cells was disrupted by SDS, suggesting that nickel ions do not function as classical bifunctional crosslinking agents. Since regulation of DNA replication and gene expression is dependent upon DNA-protein interactions, the effect of nickel in altering the extent of DNA-protein binding may interfere with this regulation and may contribute to the carcinogenic activity of nickel compounds.

Animals↗
PubMed1986

Pathway of nickel uptake influences its interaction with heterochromatic DNA.

Exposure of intact Chinese hamster ovary cells to water-soluble NiCl2 and to particulate crystalline NiS induced a concentration-dependent incidence of chromosomal aberrations which included gaps, breaks, and exchanges. Exposure of cells to crystalline NiS particles caused a high incidence of chromatid exchanges and dicentrics and produced what appears to be an effect on the condensation state of the heterochromatic long arm of the X chromosome. Treatment of cells with NiCl2 did not cause any significant effect on the long arm of the X chromosome, and there was a much lower incidence of the dicentric type of chromosomal aberrations compared to NiS. To examine whether the fragmentation/decondensation of the long arm of the X chromosome produced by crystalline NiS particles was due to a phagocytic pathway of uptake of NiS particles, cells were treated with NiCl2-albumin complexes that had been encapsulated in liposomes. Although treatment of cells with NiCl2-albumin complexes yielded higher intracellular nickel levels than were obtained by treatment of cells with NiCl2, at comparable intracellular levels fragmentation/decondensation of the heterochromatic long arm of the X chromosome was observed when nickel (II) was delivered by way of a liposome but not when cells were treated with unencapsulated NiCl2. Ionic nickel alone irrespective of its delivery mechanism exhibited some preference for heterochromatin, since there was a higher incidence of aberrations observed in the heterochromatic centromeric region of chromosomes. These observations suggest that the pathway of delivery of Ni2+ from NiS particles may be responsible for a preferential interaction of this metal with heterochromatin leading to an effect on the condensation state/fragmentation of the heterochromatic long arm of the X chromosome.

Animals↗
PubMed1986

Transamination of L-cystathionine and related compounds by a bovine liver enzyme. Possible identification with glutamine transaminase.

A transaminase which catalyses the monodeamination of L-cystathionine was purified 1100-fold with a yield of 15% from bovine liver. The monoketoderivative of cystathionine spontaneously produces the cyclic ketimine. Other sulfur-containing amino acids related to cystathionine such as cystine, lanthionine and aminoethylcysteine were also substrates for the enzyme. The relative molecular mass of the enzyme was determined to be 94 000 with a probable dimeric structure formed of identical subunits. The isoelectric point of the enzyme was at pH 5.0 and the maximal enzymatic activity was found at pH 9.0--9.2. Kinetic parameters for cystathionine and for the other sulfur amino acids as well as for some alpha-keto acids were also determined. Among the natural amino acids tested, glutamine, methionine and histidine were the best amino donors. The enzyme exhibited maximal activity toward phenylpyruvate and alpha-keto-gamma-methiolbutyrate as amino acceptors. The broad specificity of the enzyme leads us to infer that the cystathionine transaminase is very similar or identical to glutamine transaminase.

Amino Acids↗
PubMed1986

Abdominal aneurysms in a black population: clinicopathological study.

With exclusion of vascular trauma 2182 patients (1302 black and 880 white) have been treated in our Vascular Service over a period of 3 years. Sixty black patients (4.6 per cent) and 260 white patients (29.5 per cent) presented with aneurysms of the aorta and its abdominal branches. The aneurysms in the black group were distributed as follows: 50 aortic (9 suprarenal, 41 infrarenal), 6 common iliac artery, 2 superior mesenteric and 2 renal artery aneurysms. None of the 260 aneurysms seen in white patients involved arteries other than the aorta (16 suprarenal, 244 infrarenal). In the black group there was an almost equal distribution among sexes, whereas in the white group there was a male to female ratio of 2:1. The mean age was 49.4 years among the black patients, and 67.1 years among the white patients. Surgery was performed on 47 black patients and 245 white patients. Among the black patients 16 aneurysms were atherosclerotic (34 per cent), 22 were of non-atherosclerotic origin (47 per cent) and 9 were of uncertain nature (19 per cent). Of the 22 non-atherosclerotic aneurysms 14 were due to non-specific aorto-arteritis, 4 were due to tuberculous arteritis, 2 were due to intimomedial mucoid degeneration, 1 was due to syphilitic aortitis and 1 was a mycotic aneurysm. In the white group 243 aneurysms were atherosclerotic and 2 had changes of intimomedial mucoid degeneration. All aneurysms were treated along standard surgical lines, antituberculous treatment was initiated when appropriate. It was concluded that abdominal aneurysm is an uncommon disease in black patients. When it occurs a more heterogeneous pathology can be expected with an unusually high prevalence of aorto-arteritis compared with the white population.

Adolescent↗
PubMed1986

Antagonistic effect of magnesium chloride on the nickel chloride-induced inhibition of DNA replication in Chinese hamster ovary cells.

The degree of inhibition of semiconservative DNA replication induced by nickel chloride (NiCl2) was analyzed by radiolabeled-thymidine incorporation alone or with cesium chloride (CsCl) density gradient centrifugation. The onset and duration of this Ni2+-induced inhibition was time- and concentration-dependent, but the degree of inhibition was not. A maximal reduction in the rate of DNA synthesis was observed within the first hour of treatment with 2.5 mM NiCl2, which was the highest noncytotoxic concentration utilized. After six hours, 500 microM and 1 mM as well as 2.5 mM NiCl2 all produced the same 50% to 60% reduction in [3H]-thymidine incorporation into DNA. The inhibitory effect of nickel ions on DNA synthesis was reversible. The rate of DNA synthesis following a 500 microM or 1 mM NiCl2 treatment began to increase after washout of nickel, but a six-hour exposure of cells to 2.5 mM NiCl2 produced a sustained 50% to 60% suppression of DNA synthetic activity for at least 36 hours. At all concentrations of NiCl2 used in this study, some inhibition of DNA synthesis persisted for at least 48 hours, but by 72 hours after treatment, the rate of [3H]-thymidine incorporation was actually 10% above the control. Examination of autoradiographic slides of cells treated with 2.5 mM NiCl2 for six hours demonstrated a 60% reduction of silver grains, but there was no preferential reduction in the quantity of grains in the nucleolus or any other region. Cesium chloride density gradient analysis of the replication of nucleolar DNA in cells treated with 2.5 mM nickel supported the autoradiographic findings. The inhibitory effect of NiCl2 on DNA replication was prevented by the addition of magnesium chloride (MgCl2) to cells maintained in a simple salts/glucose medium (SGM). This effect did not appear to be due to an antagonism of the cellular uptake of nickel by Mg2+, since the maximally effective dose of Mg2+ reduced 63Ni2+ uptake by no more than 25% while the inhibition of replication was completely reversed.

Animals↗
PubMed1986

Distribution of subgroups of noradrenaline neurons in the coeliac ganglion of the guinea-pig.

The distributions within the coeliac ganglion of different chemically coded subgroups of noradrenaline neurons, and the relationships between these neurons and nerve fibres projecting to the ganglion from the intestine, have been assessed quantitatively by use of an immunohistochemical double-staining method. Noradrenaline (NA) neurons made up 99% of all cell bodies. Of these, 21% were also reactive for somatostatin (NA/SOM neurons), 53% were also reactive for NPY (NA/NPY neurons), and 26% were not reactive for either peptide. NA neurons without reactivity for any of the peptides whose localization was tested have been designated NA/-. A small percentage, about 1%, of neurons were reactive for both NPY and SOM. The three major types of NA neurons were arranged in clumps or ribbons throughout the ganglia, with a tendency for NA/SOM neurons to be medial and NA/NPY neurons to be lateral in the ganglia. A small group of neurons (less than 1%) encoded with dynorphin, NPY and vasoactive intestinal peptide (VIP) was encountered. VIP-immunoreactive nerve terminals, projecting to the ganglion from cell bodies in the intestine, ended around NA/SOM and NA/- neurons but not around NA/NPY neurons. Thus, the VIP axons from the intestine end selectively around neurons that modify intestinal function (NA/SOM and NA/- neurons) but not around neurons, the terminals of which supply blood vessels (NA/NPY neurons).

Animals↗
PubMed1986

Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons.

The innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine-beta-hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 micron) than those with both DBH-LI and NPY-LI (median diameter 20 micron). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI co-eluted with porcine NPY (1-36) and synthetic SP (1-11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.

Adrenergic Fibers↗
PubMed1986

Effects of noradrenaline and somatostatin on basal and stimulated mucosal ion transport in the guinea-pig small intestine.

Noradrenaline (NA) and somatostatin (SOM) stimulate intestinal water and ion absorption and are found in mucosal nerve fibres and nerve terminals in submucous ganglia of the guinea-pig small intestine. As the main projection of submucous neurons is to the mucosa, NA and SOM might alter mucosal transport either by a direct effect on the epithelium or indirectly, by affecting submucous neurons. In this study these two possible sites of action of NA and SOM have been investigated in mucosa-submucosa preparations of guinea-pig ileum. In addition, the actions of NA and SOM on the secretory responses caused by stimulation of different populations of submucous neurons have been studied. The stimulants of secretion used were a nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10(-5) M), 5-hydroxytryptamine (5-HT, 10(-7) M) and electrical field stimulation (EFS), which activate cholinergic, noncholinergic and mixed populations of submucous secretomotor neurons, respectively. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (Isc) was measured as an indication of net active ion transport across the tissue. NA (greater than or equal to 10(-8) M) and SOM (greater than 10(-10) M) each caused a decrease in Isc, indicating a net increase in ion absorption. The NA response was abolished and the magnitude of the SOM response was reduced to 20% by tetrodotoxin (10(-7) M). DMPP, 5-HT and EFS each stimulated nerves that increased Isc and each of these responses was significantly diminished by NA and SOM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract.

Eight smooth muscle preparations from the stomach, small intestine and large intestine of the guinea-pig were used to compare apamin's actions in reducing the effectiveness of transmission from enteric inhibitory nerves and in reducing responses to inhibitory agonists alpha, beta-methylene ATP, VIP and isoprenaline. The effects of apamin on inhibitory reflexes in the ileum and colon were also evaluated. Apamin had little or no effect on responses to VIP and isoprenaline in any region, but consistently and substantially reduced responses to alpha, beta-methylene ATP. Responses to stimulation of enteric inhibitory neurons were substantially reduced by apamin in the antrum circular muscle, ileum longitudinal and circular muscle, taenia coli and distal colon longitudinal muscle, but it was ineffective in the fundus circular muscle, proximal colon longitudinal muscle and distal colon circular muscle. It caused a small reduction of the relaxation of the ileal circular muscle caused reflexly by distension, but did not modify the similar descending inhibitory reflex in the circular muscle of the colon. It is concluded that apamin can be used to distinguish two types of non-noradrenergic transmission from enteric inhibitory nerves to gastrointestinal muscle. Furthermore, neither VIP nor ATP can be the sole transmitter chemical released from enteric inhibitory neurons throughout the gastrointestinal tract.

Adenosine Diphosphate↗
PubMed1986

A grading model for stress urinary incontinence.

A classification of stress incontinence is described. The stress test makes it possible to diagnose sphinctero-urethral incompetence and to identify the cases that are objectively negligible. Thus, surgical treatment can be limited to those who require it.

Abdomen↗
PubMed1986

Assessment of the uptake and mutagenicity of nickel chloride in salmonella tester strains.

NiCl2 was examined for mutagenic activity in a number of Salmonella tester strains. Conditions were established where there was substantial uptake of the metal into the bacterial cells. However, even when the metal ion was apparently taken up, as determined by metal association with cells, there was a lack of mutagenic activity. These results suggest that nickel is unable to induce basepair or frameshift mutations in Salmonella tester strains and are discussed in relationship to the low binding affinity of Ni(II) for DNA.

Chromates↗
PubMed1986

Partial depletion of neuropeptide Y from noradrenergic perivascular and cardiac axons by 6-hydroxydopamine and reserpine.

The effects of 6-hydroxydopamine (6-OHDA) and reserpine on the storage of neuropeptide Y (NPY) in noradrenergic cardiovascular nerves were examined with both immunohistochemistry and radioimmunoassay (RIA). Immunohistochemical double-labelling techniques demonstrated that NPY was located only in noradrenergic axons in the guinea-pig carotid artery, mitral valve, thoracic inferior vena cava, thoracic aorta, superior mesenteric artery and small saphenous vein. Treatment with 6-OHDA in vivo eliminated noradrenergic, NPY-containing axon terminals from all tissues, but preterminal axons were still prominent in the superior mesenteric artery. The greatest depletion of NPY detected by RIA after 6-OHDA treatment was found in tissues with a predominance of terminal noradrenergic axons, such as the small saphenous vein, whereas NPY accumulating in preterminal axons masked the loss of NPY from terminal axons in the superior mesenteric artery. After treatment with doses of reserpine that led to a rapid depletion of noradrenaline (NA) from perivascular nerves, NPY was still detected histochemically at all times although levels sometimes appeared to be reduced. RIA demonstrated that the partial depletion of NPY after reserpine consisted of a rapid phase seen in the vena cava and saphenous vein after the highest doses, and a slower phase of NPY depletion from all tissues after all doses of reserpine. The greatest depletion of NPY from terminal axons by reserpine (in small saphenous vein) was 85-90%. These results demonstrate that some NPY can be stored in noradrenergic perivascular axons in the absence of noradrenaline, but that partial depletion of NPY from axon terminals results when NA stores are depleted by reserpine. The variation in extent of NPY depletion between tissues after drug treatments can be explained by variation in the ratio of preterminal to terminal axons.

Animals↗
PubMed1986

Incidence and localization of sister chromatid exchanges induced by nickel and chromium compounds.

Carcinogenic nickel compounds enhanced the incidence of sister chromatid exchanges (SCEs) in a concentration-dependent fashion in intact Chinese hamster ovary cells. There was a preferential induction of these exchanges in the heterochromatic regions of the chromosomes. CaCrO4 also caused a dose-dependent induction of SCEs. However, in contrast to NiCl2, the exchanges induced by CaCrO4 were not localized in any particular chromosomal region. The total incidence of exchanges was higher with CaCrO4 than with NiCl2. CaCrO4, crystalline NiS and NiCl2 enhanced the incidence of SCEs at concentrations below the threshold of DNA damage as detected by the technique of alkaline elution. Additionally, following treatment time intervals of 24-48 h, there was an increase in SCEs at concentrations of NiCl2 or CaCrO4 that produced little disruption of cell cycle progression. These results are consistent with the hypothesis that potently carcinogenic nickel compounds which are not very mutagenic exert selective effects on genetically inactive heterochromatin, while potently mutagenic and carcinogenic chromate do not appear to produce a similar predominance of SCEs in heterochromatic regions.

Cell Cycle↗
PubMed1986

Electrophysiological analysis of projections of enteric inhibitory motoneurones in the guinea-pig small intestine.

The projections of neurones that produce inhibitory junction potentials (i.j.p.s) have been analysed in the small intestine of the guinea-pig. Intracellular microelectrodes were used to record i.j.p.s in circular muscle cells in response to stimulation with pairs of electrodes placed parallel to or across the length of the intestine (longitudinal and transverse electrodes, respectively). In preparations of circular muscle with the myenteric plexus attached, the mean amplitude of i.j.p.s recorded 9 mm lateral to longitudinal electrodes was about 70% of that seen at 1 mm; however, in the presence of hexamethonium (400 microM) the amplitude fell more rapidly to about 40% at 9 mm. The decline was even steeper in preparations of circular muscle from which the myenteric plexus had been removed, with the amplitude falling to 10% at 9 mm. I.j.p.s were detected up to 30 mm anal to stimuli applied with transverse electrodes in the presence of hexamethonium, but the decline was more rapid on the oral side, with i.j.p.s being detected only up to 12 mm oral to the stimulus. Nerves that travel through or originate in the myenteric plexus were severed or removed in operations performed 2-7 days before tissue was taken. 2-3 days after removal of a circumferential strip of myenteric plexus, i.j.p.s could not be recorded from the underlying circular muscle. I.j.p.s evoked by longitudinal electrodes were recorded in an area between two circumferential cuts through the myenteric plexus, 1.5-8 mm apart, 3-7 days after an operation. In this region, the i.j.p.s were significantly smaller than normal although amplitudes of up to 95% of control were measured. The consequences of single circumferential cuts through the myenteric plexus were examined 3 and 7 days after operation. Longitudinal electrodes were used to stimulate surviving fibres. Small i.j.p.s were recorded on the anal edge of the lesion; the amplitude recovered to 56% of normal in the first 2 mm on the anal side and the amplitude slowly returned to normal at 20 mm anal. On the oral side there was slight reduction in amplitude at 0.5 and 1 mm, but at greater distances amplitudes were normal. It is concluded that the simplest explanation of these results is that two populations of i.j.p.-producing neurones have their cell bodies in the myenteric plexus. Many axons supply the circular muscle close to or just anal to their cell bodies, and others run for various distances up to 30 mm in the anal direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Synaptic inputs to immunohistochemically identified neurones in the submucous plexus of the guinea-pig small intestine.

1. Electrophysiological recordings were made from neurones in the submucous plexus of the guinea-pig small intestine, and these neurones were classified according to their synaptic inputs. 2. The neurones from which recording were made were filled during the recording period with the fluorescent dye, Lucifer Yellow, so they could be re-identified after processing for immunohistochemical localization of vasoactive intestinal peptide (VIP). 3. The presence or absence of VIP-like immunoreactivity was determined for a total of 130 neurones whose synaptic inputs had been fully characterized and eighty-two were found to be VIP reactive. After the VIP reactivity had been assessed, the preparations were reprocessed to reveal immunoreactivity for neuropeptide Y (NPY) and a further twenty-three neurones (none of which were reactive for VIP) were found to be reactive for this peptide. Of the remaining twenty-five neurones, nineteen were not reactive for either VIP or NPY and six could not be re-identified after reprocessing. 4. Electrical stimulation of internodal strands evoked excitatory synaptic potentials lasting 20-30 ms (fast responses) in all but one of the 130 neurones studied. 5. Almost all the VIP-reactive neurones (seventy-eight of eighty-two cells) exhibited inhibitory synaptic potentials, ranging in amplitude from 2 to 30 mV and lasting 150-1500 ms, but few of the VIP-negative neurones had such responses (six of forty-eight cells). No inhibitory synaptic potentials could be evoked in any of the NPY-reactive neurones. 6. Most VIP-reactive neurones (sixty-nine) had a slow excitatory synaptic potential which could be evoked by a single stimulus, lasted 5-20 s and was associated with an increase in input resistance. Only one NPY-reactive neurone had a slow excitatory potential, but such potentials were seen in nine of the nineteen VIP-negative, NPY-negative neurones. 7. In nine of the twenty-three NPY-reactive neurones a single stimulus evoked an excitatory synaptic potential (intermediate excitatory synaptic potential) lasting 500-1500 ms and associated with a fall in the input resistance. None of the VIP-negative, NPY-negative neurones exhibited the intermediate excitatory potentials but it was not possible to determine whether such potentials could be evoked in VIP-reactive neurones because the inhibitory synaptic potentials would obscure such events. 8. It is concluded that neurochemically distinct populations of submucous neurones can be distinguished physiologically on the basis of the differing combinations of types of synaptic input they receive.

Action Potentials↗
PubMed1986

Effects of cholinergic blockade, adrenergic blockade and sympathetic denervation on gastrointestinal myoelectric activity in guinea pig.

Gastrointestinal myoelectric activity was recorded from conscious guinea pigs using sets of bipolar electrodes that had been surgically implanted onto the serosal surface of the gastric antrum or small intestine. The role of nerves in the control of the migrating myoelectric complex (MMC) was investigated using cholinergic and adrenergic receptor antagonists, guanethidine to block sympathetic transmission, reserpine to deplete intestinal monoamines and 6-hydroxydopamine (6-OHDA) to produce chemical sympathectomy and surgical sympathetic denervation of the stomach and small intestine. Subcutaneous infusion of hyoscine (1.0 or 3.0 mg/kg and 1.0 or 3.0 mg/kg/hr) blocked the initiation of phase 3 of the MMC. In the presence of hyoscine, intermittent electrical spiking comparable to that of phase 2 of the MMC was recorded. Hexamethonium infusion (3.0 or 10.0 mg/kg and 3.0 or 10.0 mg/kg/hr) also blocked the initiation of phase 3 and reduced the frequency of the intermittent spiking activity. Acute blockade of adrenergic receptors by simultaneous s.c. infusion of phentolamine and propranolol (1.0 mg/kg and 1.0 mg/kg/hr of each drug) did not alter the MMC, whereas infusion of guanethidine (3.75 or 7.5 mg/kg and 3.75 or 7.5 mg/kg/hr) increased the frequency of the MMC by significantly shortening the duration of phase 2. Sympathetic denervation of the stomach and small intestine did not block the MMC but decreased the cycle frequency by significantly prolonging the duration of phase 2. Chemical sympathectomy using 6-OHDA treatment (3 X 250 mg/kg s.c.) also did not abolish the MMC but decreased the frequency by increasing the duration of phase 2. Reserpine treatment (2.5 mg/kg s.c.) decreased the frequency of the MMC to a greater extent than that produced by 6-OHDA treatment. Histochemical and immunohistochemical evaluation of tissues taken from denervated, 6-OHDA- and reserpine-treated animals confirmed that surgical denervation removed sensory and adrenergic nerves to the stomach and small intestine, whereas chemical sympathectomy affected only adrenergic neurons. Reserpine treatment depleted norepinephrine from extrinsic adrenergic neurons and also depleted 5-hydroxytryptamine from intrinsic intestinal neurons. In the guinea pig, antral myoelectric activity is briefly inhibited during duodenal phase 3. Gastric inhibition persisted during duodenal phase 3 in surgically denervated animals, in 6-OHDA-treated animals and in animals treated acutely with guanethidine. These results indicate that extrinsic sensory and sympathetic nerves are not required for the initiation and propagation of the MMC in the guinea pig small intestine.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Morphine withdrawal in guinea-pig ileum is confined to one electrophysiologically defined class of myenteric neurone.

Intracellular microelectrodes were used to record changes in myenteric neurones underlying morphine dependence in the guinea-pig ileum. Of the two electrophysiologically defined classes of neurones (S and AH), only a proportion of S-neurones were involved in the naloxone-induced withdrawal responses. Withdrawal caused direct depolarization and discharge of action potentials in S-neurones and also resulted in synaptic activation of neurones of this class. Both fast and slow synaptically mediated depolarizations were evoked by naloxone. The experiments suggest that morphine withdrawal is expressed in quite specific neuronal circuits in the myenteric plexus.

Animals↗