Search results for "PAM"
showing 10 items of 1768 documents
Perivascular nerve fiber α-synuclein regulates contractility of mouse aorta: A link to autonomic dysfunction in Parkinson's disease
2010
Parkinson's disease and other neurodegenerative disorders associated to changes in alpha-synuclein often result in autonomic dysfunction, most of the time accompanied by abundant expression of this synaptic protein in peripheral autonomic neurons. Given that expression of alpha-synuclein in vascular elements has been previously reported, the present study was undertaken to determine whether alpha-synuclein directly participates in the regulation of vascular responsiveness. We detected by immunohistochemistry perivascular nerve fibers containing alpha-synuclein in the aorta of mice while aortic endothelial cells and muscular fibers themselves did not exhibit detectable levels of this protein…
Mechanism of New Antipsychotic Medications
2003
Antagonism of D 2 -like dopamine receptors is the putative mechanism underlying the antipsychotic efficacy of psychotropic drugs. Positron emission tomographic studies suggest that the antipsychotic effect of dopamine receptor antagonists occurs within a therapeutic window between 60% and 80%(striatal) D 2 receptor occupancy. The incidence of extrapyramidal side effects increases above the 80% threshold. However, the novel atypical antipsychotic drug, aripiprazole, occupies up to 95% of striatal D 2 -like dopamine receptors at clinical doses, and the incidence of extrapyramidal side effects with aripiprazole is no higher than with placebo. The most likely explanation for this finding is ari…
Antiaggressive and motor effects of the DA release inhibitor CGS 10746B
2001
In the present study the effects of a wide range of doses of the dopamine release inhibitor CGS 10746B were evaluated in spontaneous activity and in aggressive behaviour using the paradigm of isolation-induced aggression. The two higher doses (8 and 16 mg/kg) produced a decrease in spontaneous motor activity. Antiaggressive effects were observed after administration of doses from 4 mg/kg upwards. At this dose, CGS 10746B diminished threat and attack, and although an increase in immobility was observed, no impairment of other motor behaviours was presented. With higher doses, aggression was practically abolished but with a concomitant effect on many other behaviours. When animals were separa…
D2-receptor imaging with [123I]IBZM and Single Photon Emission Tomography in psychiatry: a survey of current status
1995
D2-dopamine receptors can be visualized in the human brain in vivo by Single Photon Emission Tomography (SPECT) and the radiolabeled benzamide [123I]IBZM. The present paper reviews the current status of this type of functional brain imaging with respect to basic methodological aspects, data analysis and quantification. The results from published clinical studies in different psychiatric patient populations and normal controls with [123I]IBZM are reviewed. [123I]IBZM-SPECT is a powerful tool for the investigation of D2-dopamine receptor status in psychiatric disorders, different types of drug treatment as well as therapeutic and side effects of pharmacologic agents. However, there still is a…
Regulation of the human bradykinin B2 receptor expressed in sf21 insect cells: A possible role for tyrosine kinases
2000
The functional regulation of the human bradykinin B2 receptor expressed in sf21 cells was studied. Human bradykinin B2 receptors were immunodetected as a band of 75–80 kDa in membranes from recombinant baculovirus-infected cells and visualized at the plasma membrane, by confocal microscopy, using an antibody against an epitope from its second extracellular loop. B2 receptors, detected in membranes by [3H-bradykinin] binding, showed a Kd of 0.66 nmol/L and an expression level of 2.57 pmol/mg of protein at 54 h postinfection. In these cells, bradykinin induced a transient increase of intracellular calcium ([Ca2+]i) in fura 2-AM loaded sf21 cells, and promoted [35S]-GTPγS binding to membranes.…
Relaxant effect of dopamine on the isolated rat uterus.
1988
The effect of dopamine was studied on the isolated uterus of diethylstilboestrol-treated rats. Dopamine, at concentrations (10(7)-10(-4) M) produced a concentration-dependent relaxation in the K+-depolarized rat uterus. On a molar basis, dopamine was about 500 times less potent than adrenaline in relaxing the uterus, the maximum degree of relaxation obtained with both drugs was the same. Pretreatment of the rats with reserpine (5 mg/kg) did not produce any modification of the dose-response curve to dopamine. Similarly, cocaine (3 x 10(-6) M) failed to modify the relaxant effect of dopamine. The dopamine induced relaxation was inhibited by propranolol (10(-9)-10(-7) M) in a dose-dependent ma…
Impact of serotonin 2C receptor null mutation on physiology and behavior associated with nigrostriatal dopamine pathway function.
2009
The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT2CR) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the nucleus accumbens. The influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway is less clear. Here we report that a null mutation eliminating expression of 5-HT2CRs produces marked alterations in the activity and functional output of this pathway. 5-HT2CR mutant mice displayed i…
Response to dopamine agonists of the rat isolated uterus.
1993
1. Quinpirole did not produce any effect in isolated uterus from oestrogenized rats even when it is contracted by KCl (37 mM). 2. Fenoldopam produced a relaxant effect on rat isolated uterus contracted by KCl which was not significantly modified by SCH 23390. 3. Reserpine decreased the effect of the lowest doses of fenoldopam. In reserpinized rats, propranolol (10(-9), 10(-8), 10(-7) M) antagonized the effect of the lowest doses of fenoldopam and neither SCH 23390, sulpiride nor ranitidine modified the effect of fenoldopam. 4. The results confirm our previous finding that DA1-receptors are not functional in our preparation. The effect of fenoldopam was partially due to a catecholamine-relea…
D2-dopamine receptor blockade modulates temporal resolution in goldfish.
2002
A possible effect of dopamine on the temporal resolution of goldfish was investigated in a behavioral, two-alternative, forced-choice procedure. Flicker fusion frequency (FFF) was measured before and after bilateral intravitreal injections of D1- or D2-dopamine receptor (D1-/D2-R) antagonists, or after depletion of retinal dopamine by bilateral intravitreal injections of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Prior to drug injections, fish achieved FFFs of 33–39 Hz. A D1-R antagonist, SCH 23390, reduced FFF by about 12% (P > 0.1), whereas a D2 antagonist, sulpiride, reduced the relative FFF by 25% (P < 0.03). Depletion of retinal dopamine with 6-OHDA induced a gradual…
Clorgyline effect on pineal melatonin biosynthesis in adrenalectomized rats pretreated with 6-hydroxydopamine
1994
The response to administration of the specific monoamine oxidase A (MAO-A) blocker clorgyline was investigated in adult male Sprague-Dawley rats which were adrenalectomized four days prior to treatment or were additionally sympathectomized as newborns by injection of 6-hydroxydopamine. In both groups, the contents of pineal indoles melatonin and N-acetylserotonin were augmented, and the contents of 5-hydroxyindoleacetic acid and 5-hydroxyindoletryptophol decreased 90 min following clorgyline injections when compared to rats receiving saline. The observed responses were less pronounced in rats both adrenalectomized and sympathectomized. The results are in line with the hypothesis that preser…