Ergoline derivative LEK-8829-induced turning behavior in rats with unilateral striatal ibotenic acid lesions: interaction with bromocriptine. (1/485)

LEK-8829 [9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8- aminomethylergoline bimaleinate] is an antagonist of dopamine D2 receptors and serotonin (5-HT)2 and 5-HT1A receptors in intact animals and a D1 receptor agonist in dopamine-depleted animals. In the present study, we used rats with unilateral striatal lesions with ibotenic acid (IA) to investigate the dopamine receptor activities of LEK-8829 in a model with innervated dopamine receptors. The IA-lesioned rats circled ipsilaterally when challenged with apomorphine, the mixed agonist on D1/D2 receptors. LEK-8829 induced a dose-dependent contralateral turning that was blocked by D1 receptor antagonist SCH-23390. The treatment with D1 receptor agonist SKF-82958 induced ipsilateral turning, whereas the treatment with D2 receptor antagonist haloperidol induced contralateral posture. The combined treatment with SKF-82958 and haloperidol resulted in a weak contralateral turning, indicating the possible receptor mechanism of contralateral turning induced by LEK-8829. Bromocriptine induced a weak ipsilateral turning that was blocked by haloperidol. The ipsilateral turning induced by bromocriptine was significantly potentiated by the coadministration of a low dose but not by a high dose of LEK-8829. The potentiation of turning was blocked either by SCH-23390 or by haloperidol. The potentiation of ipsilateral turning suggests the costimulation of D2 and D1 receptors by bromocriptine and LEK-8829, respectively, whereas the lack of potentiation by the highest dose of LEK-8829 may be explained by the opposing activity of LEK-8829 and bromocriptine at D2 receptors. We propose that the D2 and 5HT2 receptor-blocking and D1 receptor-stimulating profile of LEK-8829 is promising for the treatment of negative symptoms of schizophrenia.  (+info)

Dopamine receptor subtypes modulate olfactory bulb gamma-aminobutyric acid type A receptors. (2/485)

The gamma-aminobutyric acid type A (GABAA) receptor is the predominant Cl- channel protein mediating inhibition in the olfactory bulb and elsewhere in the mammalian brain. The olfactory bulb is rich in neurons containing both GABA and dopamine. Dopamine D1 and D2 receptors are also highly expressed in this brain region with a distinct and complementary distribution pattern. This distribution suggests that dopamine may control the GABAergic inhibitory processing of odor signals, possibly via different signal-transduction mechanisms. We have observed that GABAA receptors in the rat olfactory bulb are differentially modulated by dopamine in a cell-specific manner. Dopamine reduced the currents through GABA-gated Cl- channels in the interneurons, presumably granule cells. This action was mediated via D1 receptors and involved phosphorylation of GABAA receptors by protein kinase A. Enhancement of GABA responses via activation of D2 dopamine receptors and phosphorylation of GABAA receptors by protein kinase C was observed in mitral/tufted cells. Decreasing or increasing the binding affinity for GABA appears to underlie the modulatory effects of dopamine via distinct receptor subtypes. This dual action of dopamine on inhibitory GABAA receptor function in the rat olfactory bulb could be instrumental in odor detection and discrimination, olfactory learning, and ultimately odotopic memory formation.  (+info)

Kleine-Levin and Munchausen syndromes in a patient with recurrent acromegaly. (3/485)

Hypothalamic disease often affects the patients' personality and this also applies to pituitary tumors with suprasellar extension. We report on a patient with a 12-year history of recurrent acromegaly, treated with three transphenoidal operations, single field radiation therapy and bromocriptine/octreotide administration. During the course of follow-up she presented with self-inflicted anemia and Kleine-Levin syndrome (hypersomnia, hyperphagia and hypersexuality). Furthermore, she developed post-radiation necrosis within the right temporal lobe. Whether her neurological and personality disorders result - at least partially - from the acromegaly or the temporal lobe necrosis remains unclear.  (+info)

The lipoprotein profile of women with hyperprolactinaemic amenorrhoea. (4/485)

The aim of this study was to evaluate the lipoprotein profile in women with hyperprolactinaemic amenorrhoea and to establish whether effective dopamine agonist therapy might have a beneficial effect. Blood samples were collected from women with hyperprolactinaemic amenorrhoea and from controls matched for age, body mass index and smoking. Follow-up blood samples were collected from women on dopamine agonist therapy as treatment for their hyperprolactinaemia. Plasma cholesterol, high density lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein cholesterol, triglycerides, serum oestradiol and prolactin were measured. No statistically significant differences were found in the lipoprotein profile of the patient (n = 15) and control (n = 15) groups. During treatment with the dopamine agonist, bromocriptine (n = 9), significant reduction in total cholesterol [4.87 (3.98-5.87) versus 5.60 (4.55-6.61) mmol/l, P = 0.024] and LDL cholesterol [3.22 (2.01-4.23) versus 3.72 (2.59-4.93) mmol/l, P = 0.033] was noted. We conclude that beneficial alterations in the lipoprotein profile may occur in response to effective dopamine agonist therapy, presumably as a consequence of return of ovarian function and alleviation of oestrogen deficiency. Women with hyperprolactinaemic amenorrhoea should be encouraged to take effective therapy to improve their lipoprotein profile and potentially reduce their cardiovascular risk.  (+info)

Tonic dopamine inhibition of L-type Ca2+ channel activity reduces alpha1D Ca2+ channel gene expression. (5/485)

Hormones and neurotransmitters have both short-term and long-term modulatory effects on the activity of voltage-gated Ca2+ channels. Although much is known about the signal transduction underlying short-term modulation, there is far less information on mechanisms that produce long-term effects. Here, the molecular basis of long-lasting suppression of Ca2+ channel current in pituitary melanotropes by chronic dopamine exposure is examined. Experiments involving in vivo and in vitro treatments with the dopaminergic drugs haloperidol, bromocriptine, and quinpirole show that D2 receptors persistently decrease alpha1D L-type Ca2+ channel mRNA and L-type Ca2+ channel current without altering channel gating properties. In contrast, another L-channel (alpha1C) mRNA and P/Q-channel (alpha1A) mRNA are unaffected. The downregulation of alpha1D mRNA does not require decreases in cAMP levels or P/Q-channel activity. However, it is mimicked and occluded by inhibition of L-type channels. Thus, interruption of the positive feedback between L-type Ca2+ channel activity and alpha1D gene expression can account for the long-lasting regulation of L-current produced by chronic activation of D2 dopamine receptors.  (+info)

Reduction of plasma gonadotropin levels and pituitary tumor size by treatment with bromocriptine in a patient with gonadotropinoma. (6/485)

A pituitary tumor with suprasellar extension was found by magnetic resonance imaging (MRI) in a male with diabetes mellitus. Endocrine examination revealed high plasma follicle-stimulating hormone (FSH) and alpha-subunit levels, which increased with administration of thyrotropin (TSH)-releasing hormone (TRH). Plasma luteinizing hormone (LH) and testosterone levels were low. Pituitary gonadotropin producing tumor was diagnosed. Because the patient refused surgery, bromocriptine was administered and plasma FSH and alpha-subunit rapidly decreased; on MRI the tumor size was gradually reduced. When pituitary operation is not feasible, bromocriptine is one choice of treatment.  (+info)

Stimulation of matrix-metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression in rats by the preovulatory prolactin peak. (7/485)

Since structural luteolysis involves deterioration of tissue, the gene expression of matrix-metalloproteinase-1 (MMP-1) and the respective tissue inhibitor of this metalloprotease (TIMP-1) were measured at various times on the day of pro-oestrus and in animals in which the preovulatory prolactin surge was blocked for the duration of 3 cycles by bromocriptine. An additional group of prolactin-blocked rats received a prolactin replacement injection on the afternoon of pro-oestrus. In spontaneously pro-oestrous rats, MMP-1 and TIMP-1 gene expression increased significantly (P<0.01) prior to the occurrence of the preovulatory LH surge but simultaneously with the onset of the preovulatory prolactin surge. When prolactin release was blocked by bromocriptine for 3 cycles, no such changes were observed during the afternoon of pro-oestrus. However, an intraperitoneal injection of bovine prolactin at the time when the preovulatory prolactin surge occurs normally, increased MMP-1 and TIMP-1 gene expression (P<0.01). These results indicate that MMP-1 and TIMP-1 gene expression are stimulated by the preovulatory prolactin surge. Previous work has shown that the preovulatory LH surge activates the enzymatic cascade which leads to increased collagenase activity.  (+info)

Bromocriptine in Parkinsonism: long-term treatment, dose response, and comparison with levodopa. (8/485)

Thirty-seven patients with Parkinsonism were treated with bromocriptine 2.5-300 mg daily. Bromocriptine, alone or combined with levodopa, caused a 20-30% reduction in disability scores in 11 patients treated for one year. Tolerance did not develop during this period. Bromocriptine treatment was not of value in six patients who had previously not responded or who had lost their response to levodopa. However, in four of five patients with response swings on levodopa due to rapid changes in plasma dopa levels, the addition of bromocriptine caused a more stable response. Dose response curves to bromocriptine 12.5, 25, 50, and 100 mg and to levodopa 250, 500, 1000, and 2000 mg were studied in seven patients. Levodopa 2 g had a greater therapeutic effect and caused a greater rise in plasma growth hormone concentration than bromocriptine 100 mg. Levodopa caused emesis more commonly and hallucinations less commonly than bromocriptine. Bromocriptine appears to be a less potent stimulant than dopamine, and has both pre- and post-synaptic effects. Metoclopramide 60 mg oral was given 30 minutes before bromocriptine or levodopa to establish whether this caused dopamine-receptor blockade. Metoclopramide acted as a competitive antagonist to the anti-Parkinsonism and growth hormone effect of both drugs and in individual cases prevented emesis and hallucinations. The fall in blood pressure due to bromocriptine or levodopa was not antagonised by metoclopramide. Central and peripheral vascular dopamine receptors may be different in nature.  (+info)

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