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M O Carruba

Publications and source records attributed to M O Carruba.

At least 55 records · Page 3Linked to original sources
PubMed1989

Angiotensin II differentially affects cyclic AMP formation in intact adrenal glomerulosa cells and in purified membrane preparations.

In the present study we have investigated the cyclic AMP (cAMP) responses to angiotensin II (AII) in isolated rat adrenal glomerulosa cells and in purified membrane preparations. When cells were incubated with 10 nM AII cAMP cellular content increased 2-fold at 5 min and 3-fold at 10 min, then rapidly declined. The effect of AII was dose-dependent with EC50 of 4 nM and was mediated by AII receptors as shown by the pharmacological characterization with AII analogs and AII receptor antagonists. Since AII inhibited cAMP formation in purified adrenal cortical membrane preparations, the stimulatory effect observed in intact cells could be indirect and mediated by other intracellular events.

Adenylyl Cyclases↗
PubMed1989

Dopaminergic receptor mechanisms modulating the renin-angiotensin system and aldosterone secretion: an overview.

Several studies suggested that dopamine may be one of the inhibitory modulators of aldosterone secretion. Metoclopramide, a selective antagonist for dopamine D-2 receptors, increases both basal plasma aldosterone levels and the aldosterone response to angiotensin II (Ang II) in rats and humans kept on a high sodium intake, these effects being blocked by dopamine infusion. Dopamine, which has no significant effects on Ang II-induced aldosterone secretion in sodium-replete subjects, inhibits the hormonal response to Ang II infusion in sodium-depleted normal subjects, suggesting that the sodium balance state may be an important factor in the dopaminergic mechanisms controlling aldosterone secretion. The effect of dopamine on the hormone production is mediated by D-2 receptors in the adrenal cortex as shown by in vitro studies with isolated adrenal glomerulosa cells. Clinical studies have shown that dihydroergotoxine, a selective D-2 agonist, suppresses the aldosterone secretion induced by sodium depletion in hypertensive patients, an effect blocked by sulpiride. This mechanism could be of relevant therapeutic interest in its contribution to the natriuretic effects of dopaminergic agonists, which have clinical applications in the treatment of hypertension and congestive heart failure.

Adrenal Glands↗
PubMed1988

Identification and characterization of postsynaptic D1- and D2-dopamine receptors in the cardiovascular system.

Measuring adenylate cyclase activity (AC) as a biochemical index of dopamine (DA) receptor function, we obtained evidence for the presence in rabbit vasculature of both D1 receptors associated with stimulation of AC and of D2 receptors coupled with AC in an inhibitory way. The cAMP generating system in rabbit mesenteric artery was stimulated by DA and several DA agonists, an effect antagonized by the D1-receptor blocker SCH 23390 and by other neuroleptic drugs. When activation of D1 sites was impeded by SCH 23390, DA, (-)apomorphine, and (-)NPA inhibited cAMP formation. In addition, selective D2 agonists inhibited basal AC activity even when there was no D1-receptor blockade. The relative order of potency of various neuroleptics in antagonizing bromocriptine-induced inhibition of AC confirmed the D2 nature of these binding sites. Inhibition of AC activity elicited by bromocriptine remained unchanged after chemical sympathectomy, suggesting that vascular D2 receptors inhibiting AC activity are located postsynaptically in the arterial wall.

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↗
PubMed1987

Striatal adenylate cyclase-inhibiting dopamine D2 receptors are not affected by the aging process.

Radioreceptor binding studies with various labelled ligands and positron emission tomography have revealed a decline in D2 receptor concentration with age in both animal and human caudate nucleus. In this study we found that during senescence the functional characteristics of D2 receptors that inhibit adenylate cyclase (AC) are unchanged, by measuring the extent of inhibition of AC activity by dopamine mimetic drugs as a direct indicator of D2 receptor function.

Adenylyl Cyclase Inhibitors↗
PubMed1987

Effects of diethyl ether, halothane, ketamine and urethane on sympathetic activity in the rat.

The present paper describes the effects of different general anaesthetics on plasma catecholamine (CA) concentrations taken as biochemical index of peripheral sympathetic activity. In chronically catheterized rats, diethyl ether, ketamine and urethane increased plasma adrenaline (A) and noradrenaline (NA) concentrations, indicating that these drugs stimulate both neurosympathetic and adrenomedullary functions. These effects appear to be centrally mediated, since ganglionic blockade or spinal transection completely counteracted the diethyl ether- and ketamine-induced increases in plasma CA levels. Halothane induced a transient decrease in circulating A and an increase in NA. These results support the concept that general anaesthetics may have different effects on sympathetic function. Arterial blood pressure and heart rate were also measured to look for possible correlations with peripheral sympathetic activity. The enhanced release of peripheral CAs seemed to be the determining factor for increasing blood pressure and heart rate with ketamine only. In the other instances the activation of the peripheral sympathetic system appeared to maintain homeostasis by counterbalancing the various depressive effects of anaesthetics on the cardiovascular system.

Anesthetics↗
PubMed1987

Modification of the function of D1 and D2 dopamine receptors in striatum and nucleus accumbens of rats chronically treated with haloperidol.

With the aim of evaluating the possible functional modifications of both D1 and D2 dopamine receptor subpopulations after repeated administration of neuroleptics, the ability of selective D1 and D2 dopamine agonists to stimulate or inhibit, respectively, the activity of adenylate cyclase in the striatum and nucleus accumbens of rats treated with either saline or haloperidol for 21 days, was studied. It was found that stimulation of the activity of adenylate cyclase elicited by the selective D1 receptor agonist SKF 38393 was significantly greater in homogenates of striatum in rats treated with haloperidol, than in those of saline-treated rats. Similarly, the inhibitory effect on the activity of the enzyme elicited by the selective D2 agonist bromocriptine was much more evident in homogenates of the striatum from rats treated with neuroleptic than in those from saline-treated rats. When dopamine, sodium fluoride (NaF), or 5-guanylyl imidodiphosphate (Gpp(NH)p), were used as agonists to stimulate the activity of adenylate cyclase, the amount of cyclic AMP formed appeared the same in rats treated with haloperidol or saline. Dopamine receptors in nucleus accumbens behaved like those in the striatum in the pattern of modifications after repeated administration of haloperidol. Indeed, the inhibitory effect elicited by bromocriptine, as well as the stimulatory effect elicited by SKF 38393, was much more evident in nucleus accumbens from rats treated with haloperidol than in that from controls, whereas activation of adenylate cyclase induced by dopamine and sodium fluoride was similar in both experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

D2 dopamine receptors associated with inhibition of dopamine release from rat neostriatum are independent of cyclic AMP.

The ability of the selective D2 dopamine (DA) receptor agonist bromocriptine to inhibit potassium-induced DA release from striatal slices was measured in rats, which had been unilaterally injected with kainic acid into the left striatum, with the aim of verifying whether the central nervous system contains DA receptors whose stimulation evokes intracellular events which do not involve cyclic AMP. It was found that increasing concentrations of bromocriptine inhibited the potassium-stimulated DA release from rat striatal slices of the kainic acid-treated side with the same potency as in control slices. On the contrary, bromocriptine and the selective D1 agonist SKF 82526 completely lost the ability to inhibit or stimulate, respectively, striatal adenylate cyclase activity from the lesioned side. Our conclusion asserts that inhibition of DA release from rat striatal slices is mediated by stimulation of D2 DA receptors which are fully operative in absence of both DA-stimulated and DA-inhibited adenylate cyclase activity. These data suggest that the intracellular events that follow D2 receptor stimulation in the nigrostriatal nerve terminals may be regulated by second messengers other than cyclic AMP.

Animals↗
PubMed1986

Evidence for the presence of D2 but not D1 dopamine receptors in rat hypothalamic perifornical area.

Behavioural studies have shown that the perifornical hypothalamus (PFH) plays a fundamental role in mediating dopamine-induced anorexia. In the present report, we provide biochemical evidence for the occurrence of dopamine receptors in the PFH, but not in the paraventricular nucleus of the hypothalamus. Dopamine as well as bromocriptine, a D2 dopamine receptor agonist, strongly reduced the adenylate cyclase activity in the PFH. This inhibitory effect was reversed by haloperidol and by (-)-sulpiride, but not by (+)-sulpiride. On the contrary, the selective D1 dopamine agonist SKF 82526 was completely inactive in affecting adenylate cyclase activity. Our conclusion asserts the existence of dopamine D2 but not D1 receptors in the PFH, which therefore can be conceived as the only region in the brain where a single class of dopamine receptors is present.

Adenylyl Cyclases↗
PubMed1986

Peripheral and central mechanisms of action of serotoninergic anorectic drugs.

Several pieces of evidence indicate that brain serotoninergic systems play an inhibitory role in feeding, being specifically involved in regulating satiety and food selection. The anorectic drug fenfluramine has been shown to exert its effects by activating serotoninergic mechanisms. Since fenfluramine influences both central and peripheral serotonin stores, it is difficult to establish the relative contributions of the central and peripheral serotoninergic mechanisms in the regulation of feeding behaviour. In the present paper evidence is presented that changes in feeding come about In the present paper evidence is presented that changes in feeding come about after interventions in either the brain or the periphery. This evidence includes the observation that serotonin itself given subcutaneously causes a dose-related anorexia in rats trained to eat four hours a day, an effect antagonized not only by metergoline but also by xilamidine, a serotonin antagonist that does not cross the blood-brain barrier. Since serotonin given systemically cannot reach the brain, its effect is ascribed to the activation of peripheral mechanisms. Furthermore, as is the case with fenfluramine, subcutaneous administration of serotonin is able to completely counteract the overeating induced by the glucoprivic agents insulin and 2-deoxy-D-glucose (2-DG). It is concluded that activation of peripheral serotoninergic mechanisms is sufficient not only to reduce eating in rats trained to eat four hours a day, but also to control the hyperphagias brought about by insulin or 2-DG.

Animals↗
PubMed1986

Characterization of dopamine receptors associated with aldosterone secretion in rat adrenal glomerulosa.

Dopamine (DA) may participate in the control of aldosterone secretion. We report that two different receptors for DA are present in rat adrenal glomerulosa: D-1, associated with stimulation of adenylate cyclase, and D-2, whose action inhibits adenylate cyclase. The adenylate cyclase system was stimulated by DA (EC50, 7.2 microM) and different DA agonists. When the D-1 receptor blocker SCH 23390 was added to the incubation medium, DA elicited a dose-dependent inhibition of adenylate cyclase (IC50, 10 microM); (-)sulpiride specifically blocked this effect. Furthermore, DA blocked angiotensin II-induced aldosterone release from glomerulosa slices in vitro. This effect was prevented by (-)sulpiride, but not by SCH 23390. The results suggest that the D-2 receptor acts to inhibit the cAMP-generating system and may be physiologically involved in the regulation of aldosterone secretion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Pharmacology and biochemistry of dopamine receptors in the central nervous system and peripheral tissue.

A body of experimental and clinical data was generated over the last decade and now constitutes the basis for a new level of categorization of central dopamine (DA) receptors. Pharmacological and biochemical criteria were used in particular in our laboratories to separate those DA receptors which are linked in a stimulatory way to the enzyme adenylate cyclase and those which are not. We have indeed defined D1 and D2 receptors those DA receptors associated or unassociated to the generation of cyclic AMP, respectively. It should be stressed that the studies on DA receptors in the central nervous system and peripheral tissue were greatly facilitated following the discovery of specific agonist and antagonist drugs for the different DA receptors. As originally proposed by our group, DAergic ergot derivatives and substituted benzamides are now generally accepted as classes of drugs, endowed with agonist and antagonist properties, respectively, on DA D2 receptors. Taking into account the intracellular modifications following the interaction between DA and its own recognition sites, it can be suggested that in cerebral and peripheral tissue the recognition sites for DA are coupled to various of amplifier systems with different molecular mechanisms. According to the data presented and discussed in the text, DA D1 recognition sites appear to be linked to adenylate cyclase through a G/F protein (Ns unit) in a stimulatory way whereas DA D2 recognition sites are associated with adenylate cyclase through a G/F protein (Ns unit) in an inhibitory way or, at least in pituitary, are functionally coupled with inhibition of calcium entry into the cells.

Adenylyl Cyclases↗
PubMed1985

Identification of D-2 dopaminergic receptors in bovine adrenal cortex.

Dopamine receptors in bovine adrenal cortex have been studied by using 3H-(-)sulpiride as selective ligand. The specific binding is saturable and the Scatchard analysis reveals a single component with a Kd of 6.2 nM and a Bmax of 8 fmoles/mg protein. The characterization indicates that the binding is rapid, reversible, stereospecific, Na+ - and temperature- dependent. Moreover its pharmacological profile is superimposable to that of D-2 receptors in the striatum, thus suggesting that central and peripheral D-2 receptors are identical.

Adrenal Cortex↗
PubMed1985

Dopamine inhibition of neurotensin-induced increase in Ca2+ influx into rat pituitary cells.

In this paper, we report that the intracellular mechanism by which neurotensin stimulates prolactin release involves an increase in Ca2+ uptake by pituitary cells rather than an effect on adenylate cyclase system. In addition, dopamine can prevent neurotensin-induced calcium influx by interacting with dopamine D2-receptors which appear to be completely independent of the adenylate cyclase moiety but are coupled to calcium channels.

Adenylyl Cyclases↗
PubMed1985

Postsynaptic D1 and D2 dopamine receptors are present in rabbit renal and mesenteric arteries.

Measuring adenylate cyclase activity as a biochemical index of dopamine (DA) receptors, it was found that the selective D1 DA receptor agonist, SKF 82526, was able to stimulate the cAMP formation in rabbit renal and mesenteric arteries, an effect blocked by haloperidol and by SCH 23390. The D2 DA receptor agonist, bromocriptine, elicited a concentration-dependent inhibition of adenylate cyclase activity in both arteries of either normal or 6-hydroxydopamine pretreated rabbits, this effect being prevented by (-)-sulpiride but not by (+)-sulpiride. These data indicate that both D1 and D2 postsynaptic DA receptors, associated with stimulation or inhibition of adenylate cyclase activity, are present on the wall of rabbit renal and mesenteric arteries.

Adenylyl Cyclases↗
PubMed1985

Dopaminergic and serotoninergic anorectics differentially antagonize insulin- and 2-DG-induced hyperphagia.

The efficacy of anorectic drugs has been studied in rats made hyperphagic by injection of insulin or of 2-deoxy-d-glucose (2-DG). It was found that anorectics that act through a serotoninergic mechanism, i.e., d- and d-l-fenfluramine, p-chloroamphetamine, quipazine and fluoxetine antagonize both insulin- and 2-DG-induced overeating, while anorectics acting through the dopaminergic system, i.e., d-amphetamine, diethylpropion, lisuride, bromocriptine and mazindol, antagonize the hyperphagia induced by 2-DG but not that induced by insulin. Neither serotoninergic nor dopaminergic anorectics modified insulin-induced hypoglycaemia. The serotonin (5-HT) receptor blocker metergoline did not modify the hyperphagic response to insulin or 2-DG. The present results indicate that there are different neuronal or humoral circuits underlying the hyperphagic responses to insulin and 2-DG. In addition, these results, which show different effectiveness of anorectic drugs depending on what has provoked the hyperphagia, suggest that differences in the etiology of the hyperphagia of obese subjects must be taken into consideration when choosing therapy.

Animals↗
PubMed1985

Dihydroergotoxine decreases blood pressure in spontaneously hypertensive rats by interacting with peripheral dopamine receptors.

Dihydroergotoxine (10 micrograms/kg s.c.) decreased mean carotid blood pressure in urethane-anaesthetized spontaneously hypertensive rats but failed to modify the same parameter in normotensive rats. The effect was statistically significant 20 min after the injection and relatively long lasting (up to 90 min). Pharmacological characterization of the phenomenon indicated that it is mediated by stimulation of dopamine receptors, since pretreatment with haloperidol, cis-flupentixol but not with trans-flupentixol, completely prevent the reduction in blood pressure induced by dihydroergotoxine. Moreover, a challenge dose of dihydroergotoxine did not reduce mean blood pressure values in spontaneously hypertensive rats pretreated with domperidone or (-)sulpiride, but not with (+)sulpiride. These results suggest that the ergot derivative modifies the cardiovascular system by interaction with peripheral dopamine receptors of the DA2 type.

Animals↗