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1.
Neuropeptides ; 47(5): 315-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24035285

ABSTRACT

Due to their involvement in dependence pathways, opioid system genes represent strong candidates for association studies investigating alcoholism. In this study, single nucleotide polymorphisms within the genes for mu (OPRM1) and kappa (OPRK1) opioid receptors and precursors of their ligands - proopiomelanocortin (POMC), coding for beta-endorphin and prodynorphin (PDYN) coding for dynorphins, were analyzed in a case-control study that included 354 male alcohol-dependent and 357 male control subjects from Croatian population. Analysis of allele and genotype frequencies of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN revealed no differences between the tested groups. The same was true when alcohol-dependent persons were subdivided according to the Cloninger's criteria into type-1 and type-2 groups, known to differ in the extent of genetic control. Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population.


Subject(s)
Alcoholism/genetics , Enkephalins/genetics , Pro-Opiomelanocortin/genetics , Protein Precursors/genetics , Receptors, Opioid, kappa/genetics , Receptors, Opioid, mu/genetics , Adolescent , Adult , Aged , Case-Control Studies , Croatia , Genetic Association Studies , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Young Adult
2.
J Neural Transm (Vienna) ; 111(6): 733-8, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15168220

ABSTRACT

Indices of disturbed serotonergic neurotransmission are the most robust biological findings in suicide. Tryptophan hydroxylase (TPH) and 5-hydroxytryptamine transporter (5HTt) are the main regulators of 5HT signaling. Owing to the assumed functionality of intronic polymorphisms of TPH (218AC) and 5HTt (VNTR-2) genes, we investigated frequencies of concurrence of the TPH and 5HTt genotypes containing "lower activity" alleles (CC and 1010, respectively), in 192 suicide victims and 377 controls. Significant differences in frequencies of 5HTt and TPH genotype combinations were found between suicide victims and control subjects (p = 0.0156), with a clear dose-effect of the suspected ("lower activity") genotypes (p = 0.0046). Concurrent presence of the two, allegedly transcriptionally less active, variants of these genes seems to be in some kind of relation to the increased susceptibility to suicide.


Subject(s)
Carrier Proteins/genetics , Genetic Predisposition to Disease , Introns/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Nerve Tissue Proteins/genetics , Polymorphism, Genetic , Suicide , Tryptophan Hydroxylase/genetics , Croatia , Female , Genotype , Humans , Male , Polymerase Chain Reaction , Serotonin Plasma Membrane Transport Proteins , Suicide/ethnology
3.
Neuroimmunomodulation ; 9(2): 103-8, 2001.
Article in English | MEDLINE | ID: mdl-11549892

ABSTRACT

OBJECTIVE: The effect of serotonin (5-hydroxytryptamine; 5HT) on the in vitro proliferation of mitogen-stimulated lymphocytes was studied in primary cultures of rat spleen cells. METHODS: 5HT was added to the cultures 1 h prior to the mitogen, at final concentrations from 10(-13) up to 10(-2) M. T and B cell mitogens (concanavalin A, pokeweed mitogen and lipopolysaccharide) were used at suboptimal and optimal concentrations. The cell proliferation was measured 24-72 h after the addition of mitogen. The effect of each 5HT concentration was studied on a group of 6-12 animals and was expressed as a percentage of the control values obtained with mitogen alone. RESULTS: No significant effect of 5HT at concentrations from 10(-13) to 10(-5) M was found. At concentrations of > or =10(-4) M, a regular dose-dependent inhibition of the lymphocyte proliferation appeared, the concentration producing the half-maximal effect being 6 x 10(-4) M. The observed suppression was not due to 5HT cytotoxicity toward spleen cells. CONCLUSION: With the experimental system used, we failed to confirm an immunostimulatory effect of 5HT in the range of concentrations of its receptor sensitivities or lower, but found a clear-cut immunoinhibitory effect at higher concentrations.


Subject(s)
B-Lymphocytes/drug effects , Neuroimmunomodulation/immunology , Serotonin/immunology , Serotonin/pharmacology , T-Lymphocytes/drug effects , Animals , B-Lymphocytes/cytology , Cell Division/drug effects , Cell Division/immunology , Cells, Cultured , Concanavalin A/pharmacology , In Vitro Techniques , Male , Mitogens/pharmacology , Rats , Rats, Sprague-Dawley , T-Lymphocytes/cytology
4.
J Pineal Res ; 30(4): 243-7, 2001 May.
Article in English | MEDLINE | ID: mdl-11339514

ABSTRACT

Besides the pineal gland, melatonin is reported to be produced in a number of extrapineal sites, where it could act as an intracellular mediator or paracrine signal in addition to its endocrine effects. In view of the suggested immunoregulatory role of melatonin, we compared lymphoid organs and several other tissues of the rat for their potential to synthesize melatonin. Using the reverse transcription-polymerase chain reaction (RT-PCR) method, we determined the tissue-specific expression of mRNAs encoding two key enzymes of the melatonin biosynthesis: serotonin-N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). The minimal number of PCR cycles required to obtain a positive signal served as a measure for the abundance of a given mRNA. NAT and HIOMT mRNAs were detected in all tested tissues at high numbers of PCR cycles (40 and 45, respectively). At 35 cycles, only gut, testis, spinal cord, raphe nuclei, stomach fundus and striatum yielded positive signals for both enzymes. In conclusion, the presence of NAT and HIOMT mRNAs in a wide range of tissues corroborates and extends the notion of extrapineal melatonin synthesis. Comparatively low levels of the HIOMT messages in lymphoid organs, however, indicate a limited significance of melatonin synthesis within the immune system.


Subject(s)
Melatonin/biosynthesis , Melatonin/genetics , Acetylserotonin O-Methyltransferase/genetics , Animals , Arylamine N-Acetyltransferase/genetics , Base Sequence , DNA Primers/genetics , Gene Expression , Lymphoid Tissue/metabolism , Male , Pineal Gland/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Tissue Distribution
5.
Brain Behav Immun ; 14(3): 219-24, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10970681

ABSTRACT

Serotonin (5-hydroxytryptamine, 5-HT) has been shown to play a role in immunoregulation; however, little is known about specific subtypes of 5-HT receptors involved in peripheral immunomodulation. In the present study we used RT-PCR methods to examine the mRNA expression of 5-HT receptors in the cells of lymphoid tissues of the rat. All 13 rat 5-HT receptor genes cloned so far were examined in ex vivo isolated spleen, thymus, and peripheral blood lymphocytes, as well as in mitogen-stimulated spleen cells. Positive signals were obtained for 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT6, and 5-HT7 receptor mRNAs in all three compartments. Mitogen (ConA and PWM) stimulated cells additionally expressed mRNA corresponding to the 5HT-3 receptor subtype. In contrast, 5-HT1A, 5-HT1D, 5-HT2C, 5-HT4, 5-HT5A, and 5-HT5B mRNAs were not detected in any of the examined cell populations. These results may be useful as a starting point for future functional studies on immunomodulatory effects of 5-HT and may help to understand conflicting serotonergic effects on immune functions as found in the literature.


Subject(s)
Immune System/metabolism , Lymphoid Tissue/metabolism , RNA, Messenger/metabolism , Receptors, Serotonin/genetics , Animals , Blood Cells/metabolism , Concanavalin A/pharmacology , Lymphocytes/metabolism , Male , Pokeweed Mitogens/pharmacology , Polymerase Chain Reaction , Rats , Rats, Wistar , Spleen/cytology , Spleen/metabolism , Thymus Gland/cytology , Thymus Gland/metabolism
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