PubMed Health⌕ Search

Biomedical subjects

O Vindrola

Publications and source records attributed to O Vindrola.

29 records · Page 2Linked to original sources

Association of endogenous synenkephalin containing peptides with intracellular membranes of bovine adrenal medulla.

The association of endogenous synenkephalin and met-enkephalin containing peptides with the membrane of bovine chromaffin granules and physicochemical characteristics of this association were studied. The associated materials were only released at a non physiological pH range and this effect was enhanced with growing salt concentrations (0.5, 1.0 and 2.0 M KSCN). A higher peptide dissociation occurred with membrane solubilizing agents (SDS greater than Triton X-100 greater than digitonin). In microsomes the materials dissociated with 2 M KSCN (pH 7.4) corresponded to peptides larger than 12.0 kDa, while in granules corresponded to molecules smaller than 8.5 kDa, displaying synenkephalin and met-enkephalin immunoreactivities. These data suggest that some sequence of the C-terminal portion of synenkephalin may be responsible for the association of proenkephalin derived peptides with microsome and granule membranes.

Adrenal Medulla↗

Mitogenic activation of the human lymphocytes induce the release of proenkephalin derived peptides.

Several reports indicate that enkephalins participate in lymphocyte proliferation and several events of the immune response. It has been proposed that peptides involved in these processes may originate in the nervous system or endocrine glands. We have found that human peripheral blood lymphocytes (PBL) activated with a mitogenic agent contain and release proenkephalin derived peptides. The kinetics of met-enkephalin and cryptic products of proenkephalin in PBL activated with phytohemaglutinin (PHA) were studied. Peptides were released to the supernatant of stimulated PBL, reaching the highest values after 18 to 24 hours. The material secreted corresponds to high, intermediate and low molecular weight peptides derived from proenkephalin, displaying met-enkephalin and synenkephalin (proenkephalin 1-70) immunoreactivity. Therefore, an intrinsic lymphocytic proenkephalin system is induced by PHA and may play an important role in the regulation of the immune response.

Adult↗

Diurnal variations of IR-Met-enkephalin in the brain of pentylenetetrazol-kindled rats.

Pentylenetetrazol (PTZ) kindling was induced in male Wistar rats by daily i.p. injections of 40 mg/kg of the convulsant agent. Immunoreactive (IR)-Met-enkephalin was quantified in the amygdala, hippocampus and hypothalamus 17 days after the last stimulus, in groups of 6-7 rats, every 4 h, beginning at 08.00 h. IR-Met-enkephalin level displayed diurnal variations in brain regions of control animals. In the amygdala and the hippocampus the peptide peaked at 24.00 h and in the hypothalamus at 20.00 h; the troughs were at 08.00, 16.00 and 08.00 h, respectively. Diurnal variations were abolished in the amygdala and hypothalamus of kindled rats. In the amygdala the effect was characterized by an IR-Met-enkephalin increase at 04.00, 08.00 and 12.00 h; in the hypothalamus the peptide was enhanced at 08.00 and 12.00 h; in the hippocampus IR-Met-enkephalin increased at 12.00 h and showed a displacement of the peak during the dark phase. The results suggest that PTZ kindling in rats produces a long-lasting alteration on diurnal variations of IR-Met-enkephalin levels in limbic structures.

Amygdala↗

Differential release of enkephalin and enkephalin-containing peptides from perfused cat adrenal glands.

We have compared the enkephalin-like material derived from proenkephalin released from perfused cat adrenal glands stimulated with pilocarpine (5 X 10(-4)M) and nicotine (5 X 10(-6) M). In addition, two doses of acetylcholine (10(-5) and 10(-4) M) and 50 mM K+ were tested. Free Met-enkephalin immunoreactivity and total Met-enkephalin immunoreactivity, as determined by enzymatic digestion of large enkephalin-containing fragments, were coreleased with catecholamines. Free Met-enkephalin immunoreactivity represented 13% of total immunoreactivity for nicotinic stimulation, 46% for pilocarpine, 33% for 10(-5) M acetylcholine, 22% for 10(-4) M acetylcholine, and 16% for 50 mM K+. Analysis of the perfusate by gel filtration showed that 80% of the total Met-enkephalin immunoreactivity whose release was induced by pilocarpine was eluted in fractions corresponding to fragments of low molecular weight, whereas these fractions accounted only for 10% of the total Met-enkephalin immunoreactivity whose release was induced by nicotine. HPLC analysis of low-molecular-weight peptide fractions revealed that Met-enkephalin, Met-enkephalin-Arg-Gly-Leu, and Met-enkephalin-Arg-Phe represented 69% of total Met-enkephalin immunoreactivity whose release was induced by pilocarpine. These results indicate that selective activation of muscarinic receptors is followed by release of low-molecular-weight material, whereas nicotine application also yielded high-molecular-weight peptides. Furthermore, increasing the acetylcholine concentration from 10(-5) to 10(-4) M and using 50 mM K+ increased proportionally the high-molecular-weight peptide secretion. Results are discussed in relation to the existence of a heterogeneous population of granules either in the same cell or in different cells, containing proenkephalin-derived peptides. (ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Adrenal proenkephalin-derived peptides during postnatal development in spontaneously hypertensive rats.

Adrenal enkephalin and enkephalin-containing peptides were studied during postnatal development in normotensive (WKY) and spontaneously hypertensive rats (SHR). The effect of chronic treatment with the ganglionic blocker chlorisondamine (5 mg/kg) was also assessed. Free enkephalin immunoreactivity and total enkephalin immunoreactivity, as determined by enzymatic digestion of large enkephalin containing fragments, were quantitated in the adrenal glands at 11 days and 7, 16, and 24 weeks of age. Both total and free metenkephalin were significantly diminished in the adrenal of SHR when compared to WKY at all ages tested. The analysis of the chromatographic profile showed that SHR displayed reduced levels of high and low molecular weight materials at 11 days and 16 weeks of age; however intermediate compounds were high in the glands of these animals. Similar increased values for free met-enkephalin were found in adrenals of WKY and SHR after ganglionic blocker treatment, which means that the relative increase was larger in SHR than WKY; while for total enkephalin the relative increase and the concentration reached in SHR was about half of those presented in WKY. These and other results presented suggest that the basic alteration of the adrenal proenkephalin system of SHR may be due to a genetic reduction of proenkephalin levels. Otherwise, the free enkephalin decrease could be related to changes in nervous input to the adrenal gland.

Adrenal Glands↗

Pentylenetetrazol-induced seizures produce an increased release of IR-Met-enkephalin from rat striatum in vitro.

In this work we analyzed the immunoreactive-methionine-enkephalin (IR-Met-enkephalin) levels in several brain regions of rats sacrificed during the tonic extension, induced by acute treatment with pentylenetetrazol (PTZ). The results show an increased of IR-Met-enkephalin content in striatum but not in amygdala, hypothalamus, septum, hippocampus and cortex. To characterize whether this elevation of enkephalin levels in striatum corresponded to the releasable pool, we studied the in vitro efflux of this peptide in striatal slices of rats sacrificed during the seizures, in acute PTZ and in PTZ-kindled rats (kindling group I). In addition, PTZ-kindled rats were analyzed 24 h after the last stimulus (kindling group II). The striatal slices of acute group and kindling group I displayed a significant increase in the evoked release of IR-Met-enkephalin. However, no significant changes occurred from striatal slices of kindling group II animals. In vitro superfusion of GABA (100 microM) produced a approximately equal to 63% decrease in IR-Met-enkephalin released from striatal slices in both saline and acute PTZ-treated rats. Several studies suggest that opioid peptides may be released in the ictal phase of seizure in order to mediate some transient postictal behavior. Our results suggest that of several brain regions tested, only the striatal IR-Met-enkephalin may be released during the ictus to mediate postictal behavior in the acute PTZ treated and in PTZ-kindled rats. This effect may be regulated by the GABA system.

Animals↗

Pentylenetetrazol kindling produces a long-lasting elevation of IR-Met-enkephalin but not IR-Leu-enkephalin in rat brain.

Pentylenetetrazol (PTZ) kindling was induced in male Wistar rats by daily i.p. injections of 40 mg/kg of the convulsant agent. IR-Met-enkephalin and IR-Leu-enkephalin were quantified in several brain regions 16 days after the last stimulus. In addition other rats received another PTZ dose on the sixteenth day and the samples were analyzed 1 and 24 h later. The results showed a long-lasting elevation in amygdala, septum, hypothalamus and hippocampus of IR-Met-enkephalin only. These brain structures also showed a decrease of IR-Met-enkephalin 1 h after the PTZ-induced seizure, but reached newly elevated levels 24 h later. IR-Leu-enkephalin levels only showed a decrease in striatum 1 h after PTZ-induced convulsions. The data suggest that Met-enkephalin is related to permanent changes in brain function induced by PTZ kindling, while Leu-enkephalin may depend on the occurrence of epileptic seizures.

Amygdala↗

Brain content of immunoreactive [Leu5]enkephalin and [Met5]enkephalin after pentylenetetrazol-induced convulsions.

Wistar rats were injected daily with convulsant doses of PTZ (40 mg/kg). The brain content of immunoreactive (IR) enkephalins was measured after repetitive clonic convulsions and after the 'kindling' state was reached. In both instances we found a significant increase of IR [Leu5]enkephalin and IR [Met5]enkephalin in septum, striatum and amygdala 24 h after PTZ administration. These results support the suggestion that the peptide increase occurs with repetitive convulsions and not only after the 'kindling' state is reached.

Animals↗

Brain content of leu5- and met5-enkephalin changes independently during the development of kindling in the rat.

Brain content of leucine-enkephalin and methionine-enkephalin changes independently during kindling of the amygdala. Both peptides were measured after 4, 8, 15 and 21 days of stimulation. Leu-enkephalin showed a progressive increase during the kindling: the results on the 4th day did not differ significantly from the controls, whereas those on the 8th day displayed an increase only in the stimulated left hemisphere and those on the 15th day showed an increase in both hemispheres. This increase was also seen after 21 days of stimulation. In contrast, Met-enkephalin was not modified during the early stages of kindling, but was found to be increased after the animals had presented five or more generalized seizures. These results show that Leu-enkephalin is related to the development of kindling, whereas Met-enkephalin levels change only as a consequence of the generalized seizures.

Amygdala↗

Amygdaloid kindling enhances the enkephalin content in the rat brain.

Established amygdaloid kindling causes an increase in the immunoassayable content of both Leuenkephalin and Met-enkephalin in the rat brain. Control and sham-operated (electrode implanted but not stimulated) rats do not show statistically significant differences in brain enkephalin content, while kindled rats show a 40% enkephalin increase in both hemispheres. The present finding is in agreement with several lines of evidence and suggest that enkephalins may play a role in epileptic seizures.

Amygdala↗

Lack of response of proenkephalin A and sympathetic nervous system in chronic pain associated with lung cancer.

Since the discovery of the link between peripheral endogenous opioid peptides and pain regulation, these substances have been studied in relation to certain pain conditions. In order to elucidate the effect of chronic pain on both peripheral opioid system and sympathetic nervous activity, we assayed plasma met-enkephalin (ME), neutrophil met-enkephalin containing peptides (NMECP) and plasma free and conjugated catecholamines (CA) in lung cancer patients with chronic pain related to bone metastases and without pain. No significant difference was found in ME levels when the pain cancer group (0.36 +/- 0.06 pmol/ml) was compared to the pain-free group (0.37 +/- 0.04 pmol/ml); results were similar for NMECP levels (14.1 +/- 1.66 pmol/mg prot and 18.41 +/- 1.93 pmol/mg prot, respectively). CA levels in both groups were also similar. These results differ from those we have reported previously for acute pain, suggesting that a non-permanent painful stimulus may be necessary for peripheral opioid system stimulation.

Aged↗