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Biomedical subjects

A Członkowski

Publications and source records attributed to A Członkowski.

At least 37 records · Page 2Linked to original sources
PubMed1987

[3H]spiperone binding to lymphocyte in extrapyramidal disease and in aging.

[3H]Spiperone binding to lymphocytes in Parkinson's disease (PD), Wilson's disease (WD), and age-matched control groups was studied. In the untreated PD group, [3H]spiperone binding was lower than in young controls, but did not differ from elderly healthy persons. After treatment with levodopa, the number of [3H]spiperone binding sites increased. In WD, lower binding of [3H]spiperone compared with age-matched controls was found. However, the magnitude of the differences in [3H]spiperone binding to lymphocytes in PD was too small to permit its use as a routine indicator of the disease state or the adequacy of pharmacological treatment in individual patients. [3H]Spiperone binding to lymphocytes decreases with age. Changes in [3H]spiperone binding to lymphocytes may be a general phenomenon for all states where dopamine is depleted, including normal aging. The nature of [3H]spiperone binding to lymphocytes remains unclear. The possible influence of dopamine on immune reactivity is discussed.

Adult↗
PubMed1987

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems.

Intradermal inoculation of rats at the tail base with Mycobacterium butyricum led to the gradual development of an arthritic swelling of the limbs which peaked at 3 weeks and subsided thereafter. Arthritic rats displayed a loss of body weight, hypophagia, and hypodipsia in addition to a disruption of the diurnal rhythms of ingestive behavior and of core temperature. The activity of adenohypophyseal beta-endorphin-(beta-EP) secreting corticotrophs, in contrast to prolactin-(PRL) secreting lactotrophs, was increased in arthritic rats. Indeed, hypertrophy of the adrenal glands was seen. Arthritic rats also showed an elevation in spinal cord levels of immunoreactive dynorphin (DYN), an endogenous ligand of the kappa-opioid receptor. The paws and tail of arthritic rats showed lower thresholds in response to noxious pressure (hyperalgesia), higher thresholds in response to noxious heat (hypoalgesia), and no change in their response to noxious electrical stimulation. Neither naloxone nor ICI-154, 129 (a preferential delta-receptor antagonist) modified the responses of the paw or tail to pressure. However, MR 2266 (an antagonist with higher activity at kappa-receptors) decreased thresholds to pressure in arthritic, but not control, rats; that is, it potentiated the hyperalgesia. This action was stereospecific. None of the antagonists modified the response to heat. MR 2266 did not affect the response to pressure in rats with acute inflammation produced by yeast. Thus, the potentiation of pressure hyperalgesia by MR 2266 in chronic arthritic rats is highly selective. Arthritic rats showed a reduced response to the analgesic effect of a kappa-agonist (U-50,488H), whereas the response to a mu-agonist (morphine) was enhanced. These effects were specific to nociception in that their influence upon endocrine secretion (PRL and beta-EP) was otherwise changed. The secretion of beta-EP and PRL was stimulated by both morphine and U-50,488H, and the influence of U-50,488H upon the release of beta-EP (from the adenohypophysis) was enhanced in arthritic rats. It is suggested that polyarthritis is a complex condition entailing many changes, both behavioral and endocrinological. Further, arthritic rats cannot simply be described as "hyperalgesic": of critical importance is the nature of the nociceptive stimulus applied. The parallel alterations in spinal cord pools of DYN and kappa-receptors (see also Millan et al., 1986) and the changes in the influence on nociception of kappa-agonists and kappa-antagonists suggest an increased activity of spinal DYN. Thus, spinal kappa-receptors may play a role in the modulation of nociception under chronic pain.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

A model of chronic pain in the rat: response of multiple opioid systems to adjuvant-induced arthritis.

Chronic arthritic pain was induced by intradermally inoculating rats at the tail-base with Mycobacterium butyricum, which results in swelling, inflammation, and hyperalgesia of the joints. These symptoms peak at 3 weeks after inoculation and disappear by 10 weeks. The following changes were seen at 3 weeks. Immunoreactive dynorphin (ir-Dyn) and ir-alpha-neo-endorphin (alpha-NE) manifested comparable patterns of change. Their levels were increased in the anterior, but not neurointermediate, pituitary. The thalamus showed a rise in ir-Dyn and ir-alpha-NE, but no alterations were seen in other brain regions. In each case, cervical, thoracic, and lumbosacral sections of the spinal cord showed a rise in ir-Dyn and ir-alpha-NE: This was most pronounced in the lumbosacral region, where the magnitude of these shifts correlated with the intensity of arthritic symptoms. In addition, a moderate elevation in ir-methionine-enkephalin (ME) was seen in lumbosacral spinal cord. In brain, ir was not changed. The level of ir-beta-endorphin (beta-EP) was elevated both in the plasma and the anterior, but not the neurointermediate, pituitary. In addition, the content of messenger RNA encoding the beta-EP precursor, proopiomelanocortin (POMC), was enhanced in the anterior lobe. Thus, there was a selective activation of synthesis of beta-EP in, and its secretion from, the anterior lobe. In no brain tissue did levels of ir-beta-EP change. At 10 weeks postinoculation, the above changes were no longer apparent, indicating their reversibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Spinal cord dynorphin may modulate nociception via a kappa-opioid receptor in chronic arthritic rats.

Inoculation of rats with Mycobacterium butyricum produced an arthritis of the limbs which revealed an enhanced sensitivity to noxious mechanical pressure (hyperalgesia). Arthritic rats displayed a pronounced rise in immunoreactive dynorphin in lumbo-sacral spinal cord which correlated both with the intensity and time-course of this hyperalgesia. MR-2266, a relatively preferential antagonist at the chi-opioid receptor (at which dynorphin is considered to act) potentiated this hyperalgesia. In contrast, MR 2267 (its inactive stereo-isomer) was ineffective. Further, naloxone (a weak chi-antagonist), and ICI 154,129 (a preferential delta-antagonist) were, in each case, inactive. The data demonstrate a pronounced response of spinal dynorphin to chronic arthritic pain in the rat. In addition, they raise the possibility of a function of spinal DYN, via a chi-receptor, in the modulation of chronic arthritic pain.

Animals↗
PubMed1984

Contrasting interactions of the locus coeruleus as compared to the ventral noradrenergic bundle with CNS and pituitary pools of vasopressin, dynorphin and related opioid peptides in the rat.

The present study examines the influences of selective destruction of the locus coeruleus (LC) or of the ventral noradrenergic bundle (VB) upon discrete CNS and pituitary pools of vasopressin, dynorphin and related opioid peptides in the rat. The selectivity of the lesions was indicated by the fact that destruction of the LC strongly depressed levels of noradrenaline in the cortex in contrast to the hypothalamus, whereas destruction of the VB decreased noradrenaline in hypothalamus but not cortex. Rats sustaining VB lesions displayed a parallel depletion in neurointermediate, but not anterior, lobe levels of immunoreactive-(ir-dynorphin (DYN), ir-DYN, ir-alpha-neo-endorphin (ir-alpha-NE) and ir-vasopressin (ir-VP) whereas those of ir-Met-enkephalin (ir-ME) were unaffected. In the hypothalamus, the content of ir-DYN and ir-VP tended to rise and that of ir-DYN and ir-alpha-NE was significantly elevated, whereas that of ir-ME was not altered. LC destruction failed, in contrast, to modify levels of ir-VP, ir-DYN, ir-DYN, ir-alpha-NE or ir-ME in any of the above structures. It was found to, however, result in a depression in levels of ir-DYN and ir-alpha-NE, but not of ir-ME or ir-VP, in both the hippocampus and striatum whereas VB lesions were, in this respect, ineffective. Further, in the spinal cord, LC lesions resulted in a significant elevation in levels of ir-DYN and ir-alpha-NE in comparison to those of ir-DYN, ir-VP and ir-ME. Neither type of lesion significantly altered the content of any opioid peptide examined in thalamus, cortex, septum or midbrain. These data indicate that: the LC as compared to the VB interact differently with discrete pools of ir-DYN, ir-DYN, ir-alpha-NE and ir-VP in brain, pituitary and spinal cord; it is the VB rather than the LC which modulates the activity of magnocellular neurones projecting to the neural lobe of the pituitary; ir-DYN, ir-DYN and ir-alpha-NE are, in all tissues, regulated independently of ir-ME; levels of ir-DYN, ir-DYN and ir-alpha-NE are co-regulated with those of ir-VP in the hypothalamus-neural lobe axis but not in extrahypothalamic brain tissues nor the spinal cord; and DYN, DYN and alpha-NE might, in certain cases, be modulated differentially of one another, possibly reflecting alterations in precursor processing.

Animals↗
PubMed1984

Vasopressin and oxytocin in the rat spinal cord: distribution and origins in comparison to [Met]enkephalin, dynorphin and related opioids and their irresponsiveness to stimuli modulating neurohypophyseal secretion.

Immunoreactive-vasopressin, -oxytocin, -dynorphin, -dynorphin-(1-8), -alpha-neo-endorphin and -[Met]enkephalin were, in each case, present in greater concentrations in dorsal as compared to ventral, and lumbo-sacral as compared to cervico-thoracic, spinal cord. These differences were significantly more pronounced for vasopressin and oxytocin than for the other peptides. Lesions of the hypothalamic paraventricular nucleus depleted levels of immunoreactive-vasopressin and -oxytocin throughout the cord whereas levels of the opioid peptides therein were unaffected. In contrast, destruction of either the supraoptic or suprachiasmatic nucleus failed to change the content of immunoreactive-vasopressin, -oxytocin or any of the opioid peptides in the cord. Dehydration for 3 days depressed levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate lobe of the pituitary. In distinction, the levels of these were not modified in the spinal cord. Further, treatment with the synthetic corticosteroid, dexamethasone, elevated levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate pituitary whereas these were unaffected in the spinal cord. It is concluded that vasopressin and oxytocin in the spinal cord are predominantly derived from the paraventricular nucleus, localized in dorsal lumbo-sacral regions of the cord and insensitive to endocrinological manipulations. These pools may, thus, be modulated differently from their counterparts in the neurohypophysis and have a differing role, possibly in the control of the primary processing, autonomic or motor junctions. Further, there is no evidence from these or our prior studies for a close interrelationship of spinal cord vasopressin with dynorphin-related peptides (or oxytocin with [Met]enkephalin), likewise in contrast to the neurohypophysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Reduced binding of 3H-spiroperidol to lymphocyte in Wilson's disease.

Biochemical studies of CSF from patients with Wilson's disease (WD) have increased that alterations in the state of dopaminergic and serotoninergic systems are similar to those manifested in Parkinson's disease. Recently, the density of dopaminergic receptors on lymphocytes has been found to be diminished in Parkinson's disease. In the present study, 3H-spiroperidol binding was evaluated in lymphocytes acquired from 12 patients suffering from WD, as compared to blood donors. A significant decrease in the number of binding sites (Bmax) was observed in the lymphocytes of the WD patients. There was no clear relationship between clinical status, age and duration of the disease and the alterations in receptor density. The mechanism underlying the decrease in lymphocyte 3H-spiroperidol binding sites in WD demands clarification.

Adolescent↗
PubMed1983

Opiate receptor binding sites in human spinal cord.

Opiate receptor binding sites were analyzed in various regions of human spinal cord and compared to results obtained in spinal cord and brain of certain animals. mu-, delta- and kappa binding sites were individually monitored by the overall labeling of opiate binding sites with [3H]diprenorphine followed by the sequential elimination of binding to particular sites by the use of selective ligands. kappa-Receptors were the predominant type (approximately 50%), followed by mu-receptors (approximately 40%), and, in rather small amounts, delta-receptors. A similar proportion of receptor types was found in the spinal cord of guinea pigs.

Aged↗
PubMed1983

Structure-activity studies of dermorphin. Synthesis and some pharmacological data of dermorphin and its 1-substituted analogues.

Dermorphin and its analogues substituted at position 1 by N-acetyltyrosine, O-methyltyrosine, phenylalanine, D-phenylalanine, or alanine were obtained by solid-phase peptide synthesis. Their pharmacological effects were studied in vitro by the guinea pig ileum method and in vivo by the hot plate method, and the results were compared with those of morphine. The most pronounced activity was shown for dermorphin. A radioreceptor study showed a moderate affinity of dermorphin and its Tyr(Me)1 analogue for the opiate receptor sites from striatal homogenates.

Analgesia↗
PubMed1982

An approach to the elucidation of self-regulatory mechanism of substance P action. I. Synthesis and biological properties of pentapeptides related both to the substance P C-terminal fragment and enkephalins.

Seven pentapeptides, chemically related both to C-terminal fragment of substance P and Met-enkephalin were synthetized and their pharmacological properties were investigated. Peptides I-VI (L-amino acid residue in position 2) antagonized the inhibitory action of D-Ala2-Met-EK-NH2 on isolated vas deferens in vitro but were devoid of opiate-receptor binding activity in radioreceptor studies. Peptide VII (D-Phe2-Met-EK-NH2) exerted a weak inhibitory effect on contractions of transmurally stimulated vas deferens of rat which was abolished by naloxone (10(-8) M) and showed relatively strong but short-lasting analgesic activity in vivo. This peptide at concentration above 10(-5) M partially displaced the 3H-naloxone from its binding sites in striatal membranes. The possible existence of the neuronal substance P-enkephalin self-regulatory mechanism is discussed.

Amino Acid Sequence↗
PubMed1981

Lack of postulated opiate-receptor antagonistic properties of compound 48/80.

The previously suggested opiate-receptor antagonistic properties of compound 48/80 were checked both in vivo and in vitro. In electrically stimulated guinea pig ileum and rat vas deferens preparations compound 48/80 did not reverse the inhibition of the twitches caused either by morphine or Met5-enkephalin. In mice hot-plate test compound 48/80 did not decrease the analgesic activity of morphine. In radioreceptor studies compound 48/80 shows rather low affinity to the 3H-naloxone receptor sites from striatal homogenates of the rat, as compared to non-labelled naloxone and on the other hand it produced moderate, as compared to d-butaclamol, displacement of 3H-spiroperidol from rat striatal homogenates. The variation of composition of various polymers making compound 48/80 is suggested for explanation of obtained results.

Analgesics↗
PubMedDate not supplied

Analgesic activity of morphiceptin, beta-casomorphin-4, and deltakephalin in normotensive Wistar-Glaxo and spontaneously hypertensive rats.

The effects of intraventricular injection of beta-casomorphin-4, morphiceptin and deltakephalin (DTLET) on hot water tail flick and tail compression responses were investigated in Wistar Albino Glaxo (WAG) and spontaneously hypertensive rats (SHR). The effects of the mu agonist morphiceptin (20 nmol/rat), as assessed by the tail compression test, were significantly greater in SHR rats but did not differ between both strains when measured by tail flick latency. Opioid agonist deltakephalin (2 nmol/rat) in both tests elicited stronger analgesic effects in SHR as compared to WAG and these effects were blocked by naloxone in both tests used. beta-Casomorphin-4 exhibits moderate activity for mu receptors. In the tail flick test peptide (60 nmol/rat) produced an increase in latencies in SHR rats that was significantly greater than was observed in WAG rats. Naloxone pretreatment abolished the analgesic activity of beta-casomorphin-4 solely in the tail compression test in SHR. Analysis of the slopes of the dose-response curves seems to suggest that differences between the activity of these opioid peptides in SHR and WAG rats are based on a difference in the density and affinity of the subpopulation of the opioid receptors in these strains of rats.

Analgesia↗