Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new radioiodinated molecule, 125I-SCH 38840 (previously referred to as 125I-SCH 23982), has been recently reported to be a D-1 dopamine receptor ligand. The current study confirms and expands the characterization of both the radiolabeled and unlabeled forms of this compound, as well as describing the development of an in vivo D-1 receptor binding assay utilizing the 125I-SCH 38840. The binding of 125I-SCH 38840 to rat striatal membranes, in vitro, was saturable and exhibited a KD of 1.47 nM. Competition studies using 125I-SCH 38840 exhibited a pharmacological profile consistent with the proposal that 125I-SCH 38840 was binding to the D-1 receptor. Further studies with the unlabeled SCH 38840 demonstrated that it inhibited dopamine-stimulated adenylate cyclase with a KI of 66.1 nM, indicating that SCH 38840 was acting as a D-1 antagonist. Behavioral studies demonstrated that SCH 38840 (MED = 1.0 mg/kg, s.c.) blocked conditioned avoidance responding in rats, a measurement considered predictive of anti-psychotic activity in man. In vivo binding of 125I-SCH 38840 to rat striatum following s.c. administration was specific. Peak striatal levels were observed 1 h after injection, with measurable binding observed out to 8 h post-treatment. The displacement of the in vivo binding by unlabeled standards again suggested a D-1 selective interaction. The half-life of the in vivo binding of 125I-SCH 38840 was approximately 1.25 h, and was nearly equivalent to the half-life of the anti-CAR activity of unlabeled SCH 38840. These results clearly demonstrate the D-1 nature of SCH 38840's behavioral activity and strengthen the anti-psychotic potential of a D-1 antagonist.
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PMID:Characterization of the radioiodinated analogue of SCH 23390: in vitro and in vivo D-1 dopamine receptor binding studies. 305 Mar 44

The aim of this study was to determine the site within the brain at which inhibition of renal sympathetic nerve activity (RSNA) occurs following right atrial receptor stimulation. The atrial receptors were stimulated by inflating a balloon at the right vena cava-atrium junction and the reflex effect was observed before and during application of neurotransmitter agonists and antagonists into the paraventricular nucleus (PVN), or intrathecally to the spinal cord. Balloon inflation reduced RSNA by 29.1 +/- 3 % without changing blood pressure in anaesthetised Wistar rats. Microinjection of the GABA(A) receptor antagonist bicuculline (0.025 mM, 100 nl) into the PVN increased RSNA by 42.3 +/- 5 % and this was changed little by balloon inflation when PVN increased RSNA by 50.6 +/- 6.3 %. Microinjection of the nitric oxide synthase (NOS) inhibitors L-NAME (0.1 mM, 100 nl) or L-NMMA (0.2 mM, 100 nl) into PVN elicited increases in RSNA of 36 +/- 8 % or 54 +/- 10 %, respectively. Balloon inflation during PVN stimulation plus NOS inhibition resulted in RSNA activity of 8 +/- 4 % or -1 +/- 1 %, respectively, compared to baseline control. Baseline RSNA was similar throughout this series of tests ranging from 9.1 +/- 1.3 to 11.5 +/- 1.1 spike counts s(-1). To rule out the possibility that the atrial reflex inhibition was in part dependent on a dopamine-mediated PVN-spinal projection pathway inhibiting RSNA at a spinal locus, a dopamine D1 receptor antagonist SCH 23390 was intrathecally applied to the spinal cord. The effect of subsequent balloon inflation on RSNA was not significantly reduced. It was concluded that atrial receptor activation causes an inhibition of RSNA at the PVN and that this effect is mediated by GABA.
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PMID:Role of GABA and NO in the paraventricular nucleus-mediated reflex inhibition of renal sympathetic nerve activity following stimulation of right atrial receptors in the rat. 1271 58

As the distribution of apelinergic neurons in the brain suggests an important role of apelin-13 in the regulation of neuroendocrine processes, in the present experiments the effects of this recently identified neuropeptide on the open-field activity, the hypothalamo-pituitary-adrenal (HPA) system and the body temperature were investigated. I.c.v. administration of apelin-13 (1-10 microg) to rats caused significant increases in square crossing, rearing, plasma corticosterone release and core temperature, whereas it did not influence the spontaneous motor activity during telemetric observation. To determine the mediation of the actions of apelin, a corticotropin-releasing hormone (CRH) antagonist, the nonselective dopamine antagonist haloperidol, the selective dopamine D1 receptor antagonist SCH-23390 and the nitric oxide synthase inhibitor Nomega-nitro-L-arginine-methyl ester (L-NAME) were administered to the rats. The apelin-evoked HPA activation was diminished by preadministration of the CRH antagonist, while the dopamine antagonist and L-NAME attenuated only the square crossing and rearing induced by apelin-13. To characterize the transmission of the thermoregulatory action of apelin, animals were pretreated either with L-NAME, the CRH antagonist or with the cyclooxygenase inhibitor noraminophenazone. L-NAME and the CRH antagonist did not cause significant inhibition of the apelin-evoked increase in core temperature, while the cyclooxygenase inhibitor, applied 30 min before peptide treatment, did not prove effective in preventing the apelin-evoked thermoregulatory response, whereas when it was administered 2 h after the peptide treatment, it transiently and significantly reduced the hyperthermic response. The present data suggest that apelin-13 plays an important role in the regulation of behavioral, endocrine and homeostatic responses in the CNS, and dopamine, nitric oxide and prostaglandins seem to take part in the mediation of its effects. Since the corticosterone response could be blocked by the CRH antagonist, it is likely to be mediated through the activation of the CRH neurons.
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PMID:Behavioral, neuroendocrine and thermoregulatory actions of apelin-13. 1554 2

The interactions of dopaminergic receptors and nitric oxide (NO) with morphine-induced memory of passive avoidance have been investigated in mice. Pre-training administration of morphine (1, 3 and 5 mg/kg, s.c.) dose-dependently decreased the learning of a one-trial passive avoidance task. Pre-training administration of L-arginine, a nitric oxide precursor (50, 100 and 200 mg/kg, i.p.), alone did not affect memory formation. The drug (100 and 200 mg/kg) decreased significantly amnesia induced by pre-training morphine (5 mg/kg). Pre-training administration of L-NAME (N(G)-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (20 and 30 mg/kg, i.p.), dose-dependently impaired memory formation. In addition, co-pretreatment of different doses of L-NAME (10, 20 and 30 mg/kg) with lower dose of morphine (1 mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. Pre-training administration of apomorphine, a dopaminergic receptor agonist (0.25, 0.5 and 1 mg/kg, i.p.), alone also did not affect memory formation, but morphine-induced amnesia was significantly inhibited by pretreatment with apomorphine (0.5 and 1 mg/kg, 5 min, i.p.). On the other hand, the inhibition of morphine-induced amnesia by L-arginine (200 mg/kg, i.p.) was significantly decreased by pretreatment with different doses of dopamine D1 receptor antagonist, SCH 23390 (0.001, 0.01 and 0.1 mg/kg, i.p.) or D2 receptor antagonist, sulpiride (12.5, 25, 50 and 100 mg/kg, i.p.). However, the dopamine receptor antagonists could not affect memory formation by themselves. It may be concluded that the morphine-induced impairment of memory formation can be prevented by nitric oxide donor and, in this effect, dopaminergic mechanism is involved.
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PMID:Influence of nitric oxide on morphine-induced amnesia and interactions with dopaminergic receptor agents. 1663 Dec 14