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Biomedical subjects

M Costa

Publications and source records attributed to M Costa.

At least 559 records · Page 31Linked to original sources
PubMed1979

Evidence for the release of endogenous substance P from intestinal nerves.

The desensitization of receptors for substance P in the longitudinal muscle of the guinea-pig ileum has been studied. Receptors for substance P in the muscle became desensitized in the presence of relatively large concentrations of synthetic substance P; a desensitizing concentration of substance P of 7.5 x 10(-9) M shifted the concentration-response curve for substance P about 20-fold to the right, while a desensitizing concentration of 7.5 x 10(-8) M shifted the curve about 300-fold to the right. This desensitization appeared specific; concentration-response curves for carbachol, DMPP, 5-HT and bradykinin were not significantly affected by substance P, 7.5 x 10(-8) M. Furthermore, substance P in concentrations up to 7.5 x 10(-8) M did not modify transmission from either cholinergic nerves or enteric inhibitory nerves when these were stimulated electrically. However, hyoscine-resistant contractions produced by stimulation of nerves in the ileum at 10 Hz were abolished by exposure to concentrations of substance P of 7.5 x 10(-9) M or greater, suggesting that these nerves release a substance similar to or identical with substance P. DMPP evoked small hyoscine-resistant contractions of the ileum. These contractions were also antagonised by desensitization of receptors for substance P. Immunohistochemical studies showed substance P-like immunoreactivity in nerve terminals of both the myenteric and submucous plexuses.

Animals↗
PubMed1979

Actions of somatostatin on excitatory and inhibitory nerves in the intestine.

Isolated segments from the guinea-pig ileum and colon were used to investigate the sites of action of somatostatin on intestinal nerves and muscle. Somatostatin reduced the amplitude of the contraction caused by stimulation of cholinergic nerves in the ileum, without antagonizing receptors for acetylcholine on the muscle, which indicates that somatostatin inhibits the release of transmitter from the cholinergic nerves. Somatostatin caused the intestinal muscle to relax. The relaxation was blocked by tetrodotoxin but not by guanethidine, indicating that somatostatin stimulates enteric non-adrenergic inhibitory nerves. The threshold of concentration for these actions of somatostatin was low (2 to 6 X 10(-10) M). At higher concentrations, somatostatin caused a transient inhibition of peristaltic reflexes and it also stimulated cholinergic nerves. No evidence was obtained for a direct action of somatostatin on intestinal muscle. It is concluded that somatostatin is possibly a neurotransmitter in the intestine that is released at neuro-neuronal junctions and causes an inhibition of intestinal movements.

Animals↗
PubMed1979

Projections of intestinal neurons showing immunoreactivity for vasoactive intestinal polypeptide are consistent with these neurons being the enteric inhibitory neurons.

Experiments were performed to determine if the distribution of vasoactive intestinal peptide(VIP)-like immunoreactivity in nerve cell bodies and axons of the myenteric plexus and circular muscle of the small intestine is consistent with VIP being the transmitter of enteric inhibitory neurons. Immunoreactivity for VIP was found in nerve cell bodies of the myenteric plexus and in axons within the myenteric plexus and circular muscle. When the axons in the myenteric plexus were interrupted, there was accumulation of material showing reactivity for VIP on the oral side, indicating that the neurons project in an anal direction. The VIP-like immunoreactivity in axons which supply the circular muscle disappeared after a myectomy in which the overlying myenteric plexus was removed, but remained intact when extrinsic nerves were served. The projections of VIP neurons from the myenteric plexus to the circular muscle correspond to the expected projections of enteric inhibitory neurons determined by functional studies.

Animals↗
PubMed1979

A unique population of uranaffin-positive intrinsic nerve endings in the small intestine.

A positive uranaffin reaction was observed in the small (40-60 nm) diameter vesicles of some intestinal axons. There was no change in the number of reactive axons or the intensity of reaction after reserpine (5 mg/kg) or after interruption of axons reaching the intestine through the mesentery. The axons were found in the myenteric, submucous and deep muscular plexuses and in the circular muscle. Some uranaffin-positive axons formed synapses with neurons of the myenteric and submucous plexuses. It is concluded that these axons are not noradrenergic. The axons must represent one of the several nerve types which are known to be intrinsic to the intestine, but are as yet unidentified at an ultrastructural level. If, as has been postulated, the reaction localizes amine storage vesicles, the uranaffin-positive axons are probably the intrinsic amine-handling axons previously demonstrated histochemically.

Amines↗
PubMed1979

Noradrenergic transmission in isolated guinea-pig intestine following in vivo administration of antibodies to dopamine beta-hydroxylase.

The effectiveness of transmission from noradrenergic nerves supplying the guinea-pig ileum was evaluated in normal preparations and in preparations taken from animals injected 18 h to 4 days previously with antiserum to dopamine beta-hydroxylase. Degeneration of the nerves following the antiserum was monitored histochemically in the same preparations. A decline in the effectiveness of transmission, which paralleled the degeneration of the nerves, was observed. The earliest effects were detected at 18 h and the greatest effect was found at 2-4 days following the administration of antiserum. Binding of the antibodies has been detected as early as 6 h after injection. It is therefore concluded that binding of the antibodies to the nerves, per se, does not significantly compromise transmission, and that histochemical evidence of degeneration can be used to indicate the onset of functional deterioration of noradrenergic nerves following their exposure to antibodies to dopamine beta-hydroxylase.

Adrenergic Fibers↗
PubMed1979

The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon.

1 The sites of action of 5-hydroxytryptamine (5-HT) were examined in isolated segments of guinea-pig intestine. Mechanical records were taken from the longitudinal muscle of the ileum and proximal colon and from the circular muscle of the ileum and distal colon.2 In order to examine direct actions of 5-HT, nerve-mediated responses were blocked with tetrodotoxin (0.2 mug/ml). There was a gradient in the responsiveness of the longitudinal muscle of the ileum; in the proximal ileum it was usually unresponsive, whereas in the distal ileum about 30% of the amplitude of contraction was caused by a direct effect on the muscle. In the circular muscle from all parts of the ileum, direct effects on the muscle were weak or absent. In the distal colon, the circular muscle was almost always unresponsive to direct effects of 5-HT even when concentrations of 5-HT as great as 100 mug/ml were used. All direct actions of 5-HT on intestinal muscle were blocked by methysergide (1 mug/ml), which itself did not affect nerve-mediated responses.3 Excitatory cholinergic nerves and excitatory and inhibitory nerves which released unidentified substances were all stimulated by 5-HT. The contractions mediated through cholinergic nerves were blocked by hyoscine (0.6 mug/ml).4 Tachyphylaxis to the action of 5-HT occurred both for effects mediated through nerves and for direct effects on the muscle. Responses returned promptly after 5-HT was washed from the organ bath.5 While 5-HT blocked its own action on neural receptors, it did not antagonize the stimulation of nicotinic receptors on cholinergic neurones by 1-1 dimethyl-4-phenylpiperazinium iodide (DMPP). Moreover, pentolinium markedly reduced contractions caused by DMPP without significantly affecting responses to 5-HT. In contrast, (+)-tubocurarine, another nicotinic receptor antagonist, was effective in reducing contractions caused by 5-HT.6 Phenyldiguanide, which has been reported to antagonize the stimulant action of 5-HT on cholinergic neurones in the mouse small intestine, did not cause any significant reduction in the action of 5-HT on cholinergic neurones in the guinea-pig ileum unless a concentration of 1 mg/ml was used. However, contractions elicited by carbachol and DMPP were antagonized to a similar extent by phenyldiguanide at this concentration. Antagonism of the action of 5-HT at neural receptors by bromolysergic acid and by tryptamine was found but it was not specific, these drugs causing comparable decreases in responses to 5-HT, carbachol and DMPP.7 The present results, which show that 5-HT has little or no direct effect on the circular muscle of the ileum and colon, imply that, if 5-HT is a transmitter in enteric reflexes, it must be released from interneurones.

Animals↗
PubMed1979

Induction of sarcomas in nude mice by implantation of Syrian hamster fetal cells exposed in vitro to nickel subsulfide.

In vitro exposure of Syrian hamster fetal cells to nickel subsulfide (alpha Ni3S2) yielded positive colony assays for morphological transformation. A dose-response relationship was found between the concentration of alpha Ni3S2 and the incidence of morphological transformation. Exposures of alpha Ni3S2 induced morphological transformation at concentrations (0.1 or 1.0 microgram/ml of culture medium) which did not impair cell plating efficiency. Nickel monosulfide (NiS) did not induce morphological transformation of Syrian hamster fetal cells under the same conditions. Clones of alpha Ni3S2-transformed cells were able to grow in soft agar medium and demonstrated increased basal and induced activities of ornithine decarboxylase. Undifferentiated sarcomas developed in 26 of 27 nude mice at the site of s.c. injection of clones of alpha Ni3S2-transformed cells. No tumors developed in 19 control nude mice which were given s.c. injections of nontransformed Syrian hamster fetal cells which had not been exposed to alpha Ni3S2. This study demonstrates that fetal cells which undergo transformation following exposure to alpha Ni3S2 are capable of producing malignant tumors in nude mice.

Animals↗
PubMed1978

Aqueous aldehyde (Faglu) methods for the fluorescence histochemical localization of catecholamines and for ultrastructural studies of central nervous tissue.

Aqueous solutions combining a high concentration of formaldehyde (4%) with low concentrations of glutaraldehyde (0.5--01%) have been used to simultaneously localize amines by the formation of fluorescent products and to fix central nervous tissue for electron microscopy. The fluorescence reaction is produced by the aldehyde mixture at room temperature and the fluorescence is stable when the tissue is maintained in aqueous solution. This means that nerve cell bodies and terminal fields which contain catecholamines can be located accurately in vibratome sections at the light microscope level and, after further processing, can be examined under the electron microscope. With 1% glutaraldehyde in the aldehyde mixture, ultrastructural details are well preserved; there is no significant distortion of any component of the tissue. If vibratome or cryostat sections are dried against glass slides, the intensity of the fluorescence reaction is enhanced and the sections can be permanently mounted.

Animals↗
PubMed1978

Cyclic AMP levels and types I and II cyclic AMP-dependent protein kinase activity in synchronized cells and in quiescent cultures stimulated to proliferate.

Cyclic AMP as well as the specific activity of cyclic AMP-dependent protein kinase decreased from the first two hours after Chinese hamster ovary cells in plateau phase were stimulated to proliferate by tripsinization of confluent cultures and dilution in fresh media. From two to five hours after this stimulation, the cyclic AMP level and the specific activity of cyclic AMP-dependent protein kinase increased two-fold. There was a 40--50% increase in the degree of activation of cyclic AMP-dependent protein kinase during this same time interval. In plateau cultures prior to being stimulated to proliferate, type I cyclic AMP-dependent protein kinase was the predominant soluble form of these enzymes. At five hours after release from plateau, the predominant type of cyclic AMP-dependent protein kinase was type II. However, there was also a significant amount of type I present at this time. Types I and II cyclic AMP-dependent protein kinases were differentially detectable during the cell cycle of Chinese hamster ovary cells synchronized by mechanical selection of metaphase cells following colcemid treatment. During mitosis, type I kinase was predominant with only a small amount of type II activity detectable. The amount of activity of type I then progressively decreased as cells entered G1. During early G1, there was no detectable activity of type II kinase, but its activity increased from mid to late G1 and then decreased during the S phase. These data show a tight temporal relationship between the levels of cyclic AMP, the total cellular pool of type I and II cyclic AMP-dependent protein kinases, and the degree of activation of these kinases as cells traversed G1 toward S phase. These data suggest that the expression of each type of kinase may be important for the regulation of substrate phosphorylation during the cell cycle.

Animals↗