Drugs online research references
Mol Cell Neurosci. 1997;9(3):170-84.
Polarized expression of the antidepressant-sensitive serotonin transporter in epinephrine-synthesizing chromaffin cells of the rat adrenal gland.
Schroeter S, Levey AI, Blakely RD.
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6600, USA.
Antidepressant-sensitive serotonin (5-hydroxytryptamine, 5HT) transporters (SERTs) clear the amine from extracellular spaces in the CNS and periphery as a mechanism for transmitter inactivation and recycling. Although it is known that SERTs are preferentially expressed on basolateral domains in transfected epithelial cells, details of the transporter's membrane localization in vivo are lacking. 5HT and 5HT receptors have been identified in the rodent adrenal gland. Using SERT antagonist autoradiography, we establish the presence of antidepressant-sensitive transport sites in the rat adrenal medulla. Immunofluorescence experiments using antibodies specific for the SERT COOH and NH2 termini, for 5HT, or for catecholamine biosynthetic enzymes suggest that SERT mediates intra-cellular 5HT accumulation by epinephrine-secreting chromaffin cells. Using confocal microscopy, we establish that SERT expression is nonuniformly distributed along the plasma membrane of chromaffin cells. Notably, SERT immunoreactivity is largely absent from plasma membranes bordering smooth muscle that surrounds vascular sinusoids. Rather, SERT is highly expressed in membranes adjoining other chromaffin cells, consistent with a role for 5HT and SERT in autocrine or paracrine control of chromaffin cell physiology. SNAP-25, a t-SNARE protein implicated in neurotransmitter release, was found to colocalize with SERT. In contrast, Na,K ATPase and NCAM are uniformly distributed along the entire perimeter of chromaffin cell membranes. These findings underscore a role for 5HT and SERT in adrenal physiology, reveal unrecognized polarity of chromaffin cell plasma membranes, and warrant a consideration of common targeting mechanisms localizing amine transporters near release sites.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9245500&dopt=Abstract
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Psychopharmacology (Berl). 1997 Jul;132(1):89-94.
Platelet serotonin and [3H]paroxetine binding correlate with recurrence of suicidal behavior.
Verkes RJ, Fekkes D, Zwinderman AH, Hengeveld MW, Van der Mast RC, Tuyl JP, Kerkhof AJ, Van Kempen GM.
Department of Psychiatry, Leiden University Hospital, The Netherlands.
To distinguish state- from trait-dependent associations between serotonergic function and suicidal behavior, platelet serotonergic measures were repeatedly measured, during a 1-year follow-up, in 106 patients who had recently attempted suicide for at least a second time. A major DSM-III-R axis I diagnosis or use of antidepressants were reasons for exclusion. A higher affinity constant (KD) of platelet [3H]paroxetine binding was related to a higher risk of short-term recurrence of a suicide attempt, suggesting a state relationship. Higher levels of platelet serotonin at baseline were a significant predictor of a recurrent suicide attempt within the year of follow-up, suggesting a trait relationship. These associations held equally within the subgroup of 73 patients with a borderline personality disorder. Neither the maximum number of binding sites (Bmax) of [3H]paroxetine nor platelet monoamine oxidase activity correlated with suicidality. The observed association between indicators of platelet serotonin uptake and suicidal behavior suggests a state- and trait-dependency between suicidality and central serotonergic dysfunction.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9272764&dopt=Abstract
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J Chem Neuroanat. 1997 Jul;13(2):71-6.
Expression of serotonin transporter mRNA in rat brain: presence in neuronal and non-neuronal cells and effect of paroxetine.
Swan MC, Najlerahim AR, Bennett JP.
Department of Anatomy and Cell Biology, Imperial College School of Medicine at St Mary's, London, UK.
The expression of serotonin transporter mRNA in rat brain was-examined by in situ hybridisation. Hybridisation was observed in cells of the known serotonergic nuclei and no other neuronal populations. It was also associated with ependymal cells of the aqueduct which may indicate a specialisation of this part of the ventricular system in anatomical and neurophysiological terms. The effect of the selective serotonin reuptake inhibitor paroxetine on neuronal expression of the serotonin transporter mRNA was examined. Quantitation at the cellular level in the dorsal and median raphe nuclei was carried out by analysis of the mean number of silver grains per cell in autoradiographed sections. No significant change (P > 0.1) in serotonin transporter mRNA expression was observed following 21 day administration of paroxetine (5 mg/kg per day).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9285352&dopt=Abstract
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