PubMed Health⌕ Search

Biomedical subjects

M L Persson

Publications and source records attributed to M L Persson.

12 recordsLinked to original sources
PubMed1997

Tyrosine hydroxylase and dopamine D4 receptor allelic distribution in Scandinavian chronic alcoholics.

Associations of polymorphic genetic markers at the tyrosine hydroxylase (TH) and dopamine D4 receptor (DRD4) loci were examined in Scandinavian chronic alcoholics (n = 72) and control subjects (n = 67). Patients were divided into subgroups with regard to the presence of parental alcoholism and age of onset. Neither the TH nor the DRD4 allele distributions were significantly different when alcoholic samples were compared with control subjects. However, a tendency to high prevalence for 1 of the 5 TH alleles assayed (TH-K3) was observed in a subsample of 44 alcoholics characterized by late onset when compared with control subjects (27.3% vs. 10.6%, p = 0.041). Results suggest that no major influence on alcoholism is exerted through genes associated with the DRD4 or TH allelic markers examined.

Adult↗
PubMed1996

A search for association between schizophrenia and dopamine-related alleles.

Dopamine receptor dysfunction and altered tyrosine hydroxylase activity have both been implicated in the pathophysiology of schizophrenia. Schizophrenic patients and control subjects were examined for allele frequencies in the tyrosine hydroxylase and dopamine D2 and D4 receptor genes. No significant differences of allele or genotype frequencies were found between the two groups after adjustment for multiple comparisons. Neither were any significant relationships observed between allele frequencies and a number of clinical variables within the schizophrenic subsample. When no adjustment was made for multiple testing a few significant tendencies were obtained which warrant further research in extended patient and control materials. The results are compatible with the view that the tyrosine hydroxylase, dopamine receptor D2 and D4 gene polymorphisms examined are not of major importance in the aetiology or pathophysiology of schizophrenia.

Adult↗
PubMed1993

Suicide.

Explore the source record for details and available documents.

Adolescent↗
PubMed1990

Antinociceptive actions of alpha 2-adrenoceptor agonists in the rat spinal cord: evidence for antinociceptive alpha 2-adrenoceptor subtypes and dissociation of antinociceptive alpha 2-adrenoceptors from cyclic AMP.

The antinociceptive actions of intrathecal injections of two alpha 2-adrenergic agonists, UK-14,304 and guanfacine, were investigated in rats after pretreatment of the animals with the noradrenaline neurotoxin N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) 14 days in advance. The chronic noradrenaline depletion induced by DSP4 caused a marked increase in sensitivity of the antinociceptive action of UK-14,304 in the tail-flick test. By contrast, the antinociceptive effect of guanfacine was not appreciably affected by the DSP4 treatment. The antinociceptive effects of both UK-14,304 and guanfacine were blocked by intraperitoneal injections of yohimbine, a result indicating that both drugs induced their actions by activating alpha 2-adrenoceptors. Both UK-14,304 and guanfacine were found to reduce the production of cyclic AMP (cAMP) in the spinal cord, as determined using an in vitro radioisotopic method. The cAMP inhibitory effects of both agonists were effectively blocked by yohimbine, but not by prazosin, a finding indicating the alpha 2-adrenergic nature of the response. However, the cAMP inhibitory effect of UK-14,304 was not potentiated by pretreatment with DSP4, a finding in marked contrast with the strong potentiation of the antinociceptive action of UK-14,304 induced by the chronic depletion of endogenous noradrenaline. Moreover, intrathecal injections of forskolin, which increased the endogenous levels of spinal cord cAMP fivefold, did not modify the antinociceptive effects of UK-14,304 or guanfacine in neither normal nor DSP4-treated animals. It is suggested that there exist pharmacologically differing alpha 2-adrenergic receptor pathways capable of mediating antinociceptive effects at the level of the spinal cord. The cAMP inhibitory actions of spinal cord alpha 2-adrenoceptors appear not to be directly linked with the antinociceptive actions of these receptors.

Adrenergic alpha-Agonists↗
PubMed1988

Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.

Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia.

5,7-Dihydroxytryptamine↗
PubMed1987

Increased antinociception by alpha-adrenoceptor drugs after spinal cord noradrenaline depletion.

Animals depleted of the bulbospinal NA fiber tracts have been reported to be supersensitive to antinociceptive effects of intrathecally administered noradrenaline (NA) in vivo. In the present investigation, the antinociceptive effects were determined after systemic or intrathecal injections of noradrenergic agents. NA and the selective alpha 2-adrenoceptor agonists guanfacine and clonidine were used. NA depletion was performed by treatment neonatally with 6-hydroxydopamine (6-OHDA), or in adult animals by intrathecal 6-OHDA administration or systemic N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4). The neurotoxins were found to cause a severe depletion of spinal NA without affecting dopamine (DA) or 5-hydroxytryptamine (5-HT) levels. The antinociceptive effects of intrathecal injection of NA, clonidine and guanfacine were more strongly enhanced in the depleted than in the control rats. It was also found that clonidine and guanfacine given systemically had a stronger effect in depleted than in control animals. In conclusion, depletion of descending NA pathways induces functional supersensitivity both to intrathecally administered NA and to the selective alpha 2-adrenoceptor agonists clonidine and guanfacine. It was also found that systemically administered clonidine and guanfacine had a stronger effect in NA-depleted than in control animals.

Adrenergic alpha-Agonists↗
PubMed1987

(+)-8-OH-DPAT and 5-MeODMT induced analgesia is antagonised by noradrenaline depletion.

In experiments with both rats and mice the 5-HT agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) were shown to produce reliable analgesic effects after acute administration (1 mg/kg SC) in the tail-flick, hot-plate and shock-titration tests of nociception. Prior treatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), systemically administered to both rats and mice abolished the analgesic effects of both the 5-HT agonist compounds in all the tests of nociception used. Intrathecal 6-hydroxydopamine (6-OHDA) treatment also abolished the analgesic effects of 8-OH-DPAT and 5-MeODMT; in the tail-flick test the analgesia induced by 8-OH-DPAT was reversed to an hyperalgesia. Biochemical analyses confirmed notable noradrenaline depletions in the spinal cord. It is concluded that an important interaction between presynaptic noradrenergic terminals and serotonergic receptor sites, possibly 5-HT1A, mediates spinal nociception processes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1981

Selective inhibition by harmane of the apurinic apyrimidinic endonuclease activity of phage T4-induced UV endonuclease.

1-Methyl-9H-pyrido-[3,4-b]indole (harmane) inhibits the apurinic/apyrimidinic (AP) endonuclease activity of the UV endonuclease induced by phage T4, whereas it stimulates the pyrimidine dimer-DNA glycosylase activity of that enzyme. E. coli endonuclease IV, E. coli endonuclease VI (the AP endonuclease activity associated with E. coli exonuclease III), and E. coli uracil-DNA glycosylase were not inhibited by harmane. Human fibroblast AP endonucleases I and II also were only slightly inhibited. Therefore, harmane is neither a general inhibitor of AP endonucleases, nor a general inhibitor of Class I AP endonucleases which incise DNA on the 3'-side of AP sites. However, E. coli endonuclease III and its associated dihydroxythymine-DNA glycosylase activity were both inhibited by harmane. This observation suggests that harmane may inhibit only AP endonucleases which have associated glycosylase activities.

Alkaloids↗
PubMed1981

Evidence that the UV endonuclease activity induced by bacteriophage T4 contains both pyrimidine dimer-DNA glycosylase and apyrimidinic/apurinic endonuclease activities in the enzyme molecule.

We performed experiments to determine whether the phage T4-induced UV endonuclease activity is a single protein containing both pyrimidine dimer-DNA glycosylase and apyrimidinic endonuclease activities. The UV endonuclease activity is induced by the denV gene and codes for the glycosylase activity. We obtained several kinds of evidence that the protein containing the glycosylase activity also contains the apyrimidinic endonuclease activity. After chromatography on DEAE-cellulose, the two activities copurified during phosphocellulose chromatography and Sephadex G-100 chromatography, with a constant ratio of activities across the activity peaks. On Sephadex G-100 columns the molecular weights of the two activities agreed within 2,500 or less. When an extract of cells infected with the T4 V1 mutant was purified in exactly the same way as an extract of cells infected with T4 V1+, neither glycosylase nor apyrimidinic endonuclease activity was detected in the normal elution position of the T4 UV endonuclease activity. The glycosylase and apyrimidinic endonuclease activities were induced with similar kinetics, which were characteristic of immediate early rather than delayed early enzymes. This correlated well with the presumed major role of these activities in repairing thymine dimers in parental DNA before DNA replication begins. Finally, glycosylase and apyrimidinic endonuclease activities were lost in parallel during incubation of the enzyme at 46 degree C. Our results indicated that both of these enzyme activities are contained in the same enzyme molecule and, probably, in the same polypeptide.

DNA Glycosylases↗