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E Nisoli

Publications and source records attributed to E Nisoli.

47 records · Page 3Linked to original sources
PubMed1992

Tolerance to hypoactivity and sensitization to hyperactivity after chronic treatment with a presynaptic dose of lisuride in rats.

We studied the adaptive changes of the locomotor effects of lisuride, a selective agonist for dopamine (DA) D2 receptors, and the functional state of D1 and D2 receptors after repeated administration of lisuride at a dose supposed to act preferentially on DA autoreceptors. Rats were treated daily with saline or lisuride, at a dose that causes a significant reduction in locomotor activity when given to naive rats (25 micrograms/kg i.p.), for 33 days and the effect of different challenging doses of the drug on locomotor activity was measured at different times during and after the treatment. The functional state of D1 and D2 DA receptors was evaluated by measuring SKF 82526-stimulated and LY 171555-inhibited adenylate cyclase (AC) activity in the caudatus/putamen, nucleus accumbens and substantia nigra and naive and chronically treated rats. There was a progressive decline in the ability of lisuride to decrease locomotor activity in rats given daily injections of lisuride, and there was a marked reduction in the threshold dose of lisuride for causing hypermotility. The functional state of DA receptors, positively or negatively linked to AC activity, was not modified by the treatment. The most suitable explanation of the reported adaptive behavioral changes is a down-regulation of DA autoreceptors after chronic treatment with presynaptic doses of lisuride.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Biochemical and functional identification of a novel dopamine receptor subtype in rat brown adipose tissue. Its role in modulating sympathetic stimulation-induced thermogenesis.

Various dopamine (DA) agonists including propylnorapomorphine, lisuride, bromocriptine, apomorphine and quinpirole were found to reduce adenylate cyclase activity in rat brown adipose tissue homogenates. These inhibitory effects were antagonized, with a very low stereoselectivity, by DA receptor antagonists with the following rank order of potency: haloperidol > (+)-butaclamol > or = (-)-butaclamol >> clozapine > or = (-)-sulpiride > or = (+)-sulpiride > or = eticlopride, but not by the alpha-2 adrenoceptor antagonists, phenoxybenzamine and yohimbine or the serotonin receptor antagonists, ketanserin and metergoline. The selective D1 agonist, fenoldopam, was completely inactive in modifying the basal enzyme activity. DA as well as various DA agonists (lisuride > propylnorapomorphine > bromocriptine > apomorphine > quinpirole) dose-dependently reduced the stimulation of adenylate cyclase activity induced either by forskolin or by the beta adrenoceptor agonist, (-)-isoproterenol. Similar results were obtained also in dispersed brown adipocytes. We also found that DA and various DA receptor agonists induced a significant decrease of beta adrenoceptor-stimulated glycerol and nonesterified fatty acids release from brown adipocytes. This effect was selectively antagonized by haloperidol and butaclamol. Thus, the receptors present on the BAT membranes appear to be dopaminergic in nature although they differ from the classical D2 receptor for the following: 1) the low affinity for the most selective D2, D3 and D4 receptor agonist and antagonist (quinpirole, sulpiride and clozapine); 2) the absence of stereoselectivity for various DA antagonists (butaclamol and sulpiride); and 3) the lack of detectable mRNA encoding D2 or D3 DA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1991

Characterization of monoaminergic receptors in hypothalamic nuclei mediating feeding behavior in rats.

It has been proposed that receptors mediating the action of dopamine (DA), serotonin and norepinephrine exist in the hypothalamus to control feeding behavior in the rat. To further characterize the receptor subtypes involved in this phenomenon and determine their locus within specific hypothalamic nuclei, measurements of adenylate cyclase (AC) activity, as a biochemical index of monoaminergic receptors, were taken after administration of various monoaminergic agonists and antagonists. It was first found that DA and selective D2 agonists, such as quinpirole and lisuride, strongly reduced AC activity in homogenates from the lateral perifornical hypothalamus (PFH), where previous evidence has shown DA agonists to inhibit feeding. These inhibitory effects were stereospecifically antagonized by the D2 antagonist (-)-sulpiride. The selective D1 agonist SKF 82526, up to 100 microM, was completely inactive in modifying the basal enzyme function in PFH. In homogenates from rat paraventricular nucleus (PVN), DA (100 microM), quinpirole (10 microM) and SKF 82526 (100 microM) were unable to affect AC activity, consistent with previous pharmacological evidence showing DA in the PVN to have no effect on feeding. These results suggest the presence of D2 receptors in the PFH but not in the PVN and the absence of D1 receptors in both areas. Under the same experimental conditions, the alpha 2 adrenoceptor agonist clonidine was able to inhibit AC in the PVN, and this effect was reversed by the alpha adrenoceptor antagonist phenoxybenzamine. These results supported the previously described PVN alpha 2 adrenergic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1990

Repeated administration of lisuride down-regulates dopamine D-2 receptor function in mesostriatal and in mesolimbocortical rat brain regions.

Functional modifications of both D-1 and D-2 dopamine (DA) receptor subtypes following repeated administration of lisuride, a DA agonist that acts selectively on D-2 DA receptors were studied. The functional state of D-1 and D-2 DA receptors was evaluated from measurements of SKF 82526-stimulated and bromocriptine-inhibited adenylate cyclase activity in different brain regions of rats treated daily for 26 days with saline or lisuride (100 micrograms/kg i.p.). Persistent stimulation by lisuride of DA receptors in striatum, nucleus accumbens, substantia nigra, frontal cortex, hippocampus and pituitary gland induced a down-regulation of D-2 receptors without changing the functional activity of D-1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Repeated reserpine administration up-regulates the transduction mechanisms of D1 receptors without changing the density of [3H]SCH 23390 binding.

Behavioural studies have shown that stimulation of D1 receptors, which is uneffective in normal rats, induced strong hypermotility in rats pretreated with reserpine for 5 days. On this basis, we investigated D1 receptor plasticity using the 5-day treatment with reserpine (1 mg/kg; s.c.) as an experimental model. The function of striatal D1 receptors was determined both in binding studies with [3H]SCH 23390 and by measuring formation of cAMP in response to the selective agonist, SKF 82526. The results indicate that the responsiveness of adenylate cyclase (AC) to D1 receptor stimulation was markedly increased after reserpine administration, while no significant changes were found in [3H]SCH 23390 binding site density. Moreover, formation of cAMP after stimulation of Gs protein with GppNHp was markedly enhanced in dopamine (DA)-depleted rats; the responsiveness of AC to forskolin, which directly stimulates the AC catalytic unit, was not affected by reserpine administration. These data indicate that reserpine-induced D1 receptor up-regulation is apparently mediated by a marked enhancement of the coupling efficiency of Gs protein, suggesting that the D1 behavioral supersensitivity does not correlate with the density of D1 receptors, but is reflected by a selective up-regulation of their transduction mechanisms.

Adenylyl Cyclases↗
PubMed1988

Pharmacological characterization of D1 and D2 dopamine receptors in rat limbocortical areas. I. Frontal cortex.

The mesolimbocortical dopaminergic system innervates several brain regions including the frontal cortex. The aim of our work was both to identify and to pharmacologically characterize the dopamine receptors located in this brain area. We found that different selective agonists for D1 receptors were able to increase adenylate cyclase activity, and these effects were antagonized by haloperidol and SCH 23390. Moreover different agonists for D2 receptors inhibited the cyclic AMP generating system, and these effects were prevented by (-)-sulpiride. According to the paradigm that D1 receptors are linked with adenylate cyclase in a stimulatory way, while D2 receptors are linked with the same enzyme in an inhibitory way, our results indicate the presence of both D1 and D2 receptors in rat frontal cortex.

Adenylyl Cyclases↗
PubMed1988

Pharmacological characterization of D1 and D2 dopamine receptors in rat limbocortical areas. II. Dorsal hippocampus.

The mesolimbocortical dopamine (DA) system innervates several brain regions including the hippocampus. The aim of the present study was both to identify and to pharmacologically characterize the DA receptors located in this brain area. The results show that different agonists for D1 DA receptors, such as DA itself, SKF82526 and (-)-apomorphine, were able to increase adenylate cyclase activity, and these effects were antagonized by haloperidol and SCH 23390. Moreover bromocriptine, lisuride and RU 24213, which are agonists for D2DA receptors, inhibited the cyclic AMP generating system and these effects were prevented by (-)-sulpiride. According to the paradigm that D1 DA receptors are linked with adenylate cyclase in a stimulatory way, while D2 DA receptors are linked with the same enzyme in an inhibitory way, our results indicate the presence of both D1 and D2 receptors in rat hippocampus. Localization studies show that both DA receptor subtypes are restricted to the dorsal part of the hippocampus.

Adenylyl Cyclases↗
PubMed1987

Repeated administration of (-)sulpiride and SCH 23390 differentially up-regulate D-1 and D-2 dopamine receptor function in rat mesostriatal areas but not in cortical-limbic brain regions.

We studied the possible functional modifications of both D-1 and D-2 dopamine (DA) receptor subtypes following repeated administration of DA antagonists that act selectively on a single class of DA receptors. The functional state of D-1 and D-2 DA receptors in particular was evaluated by measuring SKF 82526-stimulated and bromocriptine-inhibited adenylate cyclase activity in different brain regions of rats treated with saline, SCH 23390, or (-)sulpiride for 21 days. The results indicate that chronic blockade of D-1 DA receptors in striatum, nucleus accumbens, and substantia nigra by SCH 23390 induced up-regulation of the D-1 receptors without changing the functional activity of D-2 receptors. Likewise, chronic blockade of D-2 DA receptors by (-)sulpiride caused up-regulation of D-2 but not D-1 DA receptors in striatum, nucleus accumbens, substantia nigra and pituitary. SCH 23390 or (-)sulpiride did not modify the functional activity of either D-1 or D-2 DA receptors located in frontal cortex and hippocampus. In conclusion, these results indicate that chronic treatment with selective D-1 or D-2 DA receptor blockers induces a receptor-specific up-regulation which involves the DA receptors located in the nigrostriatal system and pituitary but not those in the limbic-cortical areas.

Adenylyl Cyclases↗
PubMedDate not supplied

Catecholamine and serotonin depletion from rat spinal cord: effects on morphine and footshock induced analgesia.

Using a methodology that causes a selective degeneration of spinal cord catecholaminergic or serotoninergic pathways but not those of the brain, it has been possible to study more precisely the role played by the spinal cord monoaminergic systems that underly the mechanism through which morphine and endogenous opioids modulate nociceptive inputs. Both noradrenaline (NA) and serotonin (5-HT) appear to be involved: first, the noradrenergic and only subsequently, with higher doses of the opiate, the serotoninergic pathways.

5,7-Dihydroxytryptamine↗
PubMedDate not supplied

Differential relevance of beta-adrenoceptor subtypes in modulating the rat brown adipocytes function.

The potencies and intrinsic activities on cyclic AMP accumulation and lipolysis of various selective beta 3-adrenoceptor agonists were studied in brown adipocytes and compared to those of the nonselective, (-)-isoprenaline, and conventional beta 1- (dobutamine) and beta 2-adrenoceptor (salbutamol) agonists. (-)-Isoprenaline, dobutamine and salbutamol were more potent stimulants of lipolysis than of cyclic AMP accumulation, while the selective beta 3-adrenoceptor agonists had similar potencies for these two functions. Apparent pA2 values of the selective beta 1-(CGP20712A) and beta 2-adrenoceptor (ICI118551) antagonist for inhibition of adenylyl cyclase stimulation by (-)-isoprenaline and the beta 3-adrenoceptor agonists, BRL37344, SR58611A, and ICI215001, indicated that (-)-isoprenaline can stimulate the enzyme through a relevant beta 1-adrenergic component, while the other drugs activate the enzyme mainly by acting on the beta 3-adrenoceptors. On the contrary, antagonism of the lipolysis yielded apparent pA2 values for CGP20712A and ICI118551, suggesting that (-)-isoprenaline, like all the beta 3-adrenoceptor agonists, stimulated the brown adipose tissue lipid metabolism mainly through an action on beta 3-adrenoceptors.

Adipocytes↗