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Biomedical subjects

C Missale

Publications and source records attributed to C Missale.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1988

Inhibition of the aldosterone response to sodium depletion in man by stimulation of dopamine DA2 receptors.

In this study we have investigated the effect of co-dergocrine, a selective DA2-agonist, on plasma aldosterone concentrations (PAC) in twelve patients with essential hypertension both in basal conditions and during sodium depletion. Sodium depletion resulted in an increase of PAC from 38 (13) pg/ml to 297 (21) pg/ml. The PAC response to sodium depletion was reduced to 155 (29) pg/ml by co-dergocrine. No significant PAC changes were found in patients maintained on a normal sodium intake. In addition the drug did not significantly modify plasma renin activity (PRA) in either experimental group. These results suggest that the dopaminergic inhibition of aldosterone secretion in man is mediated by DA2 receptors in the adrenal cortex.

Aged↗
PubMed1988

A superfusion method for the study of calcium fluxes from pituitary cells.

This paper describes a superfusion technique that allows the study of calcium fluxes from a preparation of anterior pituitary cells. There is easy reproducibility, high sensitivity, controlled conditions that closely resemble those in vivo, possibility to operate sequential treatments on the same sample. These are some of the advantages of this method. An interesting application consists of the possibility of simultaneous measurement of calcium fluxes and hormone release.

Animals↗
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↗
PubMed1988

Vasoactive intestinal polypeptide (VIP) selectively stimulates prolactin release in healthy women.

The neuropeptide, vasoactive intestinal polypeptide (VIP), is released from the hypothalamus to the portal circulation, and experiments on animals provide evidence that it might modulate hormone secretion from the pituitary. Here we report the effects of VIP on the release of different pituitary hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyrotropin-releasing hormone (TSH), in normal women. Seven healthy women (aged 27-32; body weight 53-60 kg), with normal menses and receiving no medication, were tested on days 20-23 of their cycle. Porcine VIP was injected i.v. as a bolus dose of 1 mcg/kg body weight. Blood samples were collected 10 minutes prior to VIP administration and 5, 15, 30, 45, 60 and 90 minutes after VIP injection. Blood pressure and heart rate were continuously monitored. Hormone levels were determined by RIA. Stress, which can stimulate PRL release, was assayed by measuring the effect of placebo on hormone release (5 controls). VIP injection induced a significant (p less than 0.01) increase in plasma PRL levels. Basal PRL was 20.25 +/- 9.14 ng/ml; 5 minutes after VIP injection PRL levels rose to 45.0 +/- 14.9 ng/ml (p less than 0.01). At 15 minutes a plateau was reached (46.0 +/- 14.5 ng/ml), then the levels slowly decreased. VIP administration did not modify the plasma concentration of LH, FSH or TSH at any time during the observation period. The present study indicates that VIP might play a physiological role as a RPL-releasing factor in human beings.

Adult↗
PubMed1988

Dopamine selectively inhibits angiotensin II-induced aldosterone secretion by interacting with D-2 receptors.

Aldosterone secretion is subject to both stimulatory and inhibitory controls. Angiotensin II (AII) is the primary stimulator of aldosterone production and an inhibitory role of dopamine (DA) has been suggested recently. In this study we investigated the interactions between DA and AII in the intracellular events leading to aldosterone secretion. By measuring aldosterone secretion and cyclic AMP (cAMP) formation in intact adrenal glomerulosa cells we show that AII induced a sustained stimulation of aldosterone secretion (EC50, 0.41 nM) and a rapid and transient increase in intracellular cAMP content (EC50, 4 nM). DA inhibited both aldosterone secretion (IC50, 300 nM) and cAMP formation (IC50, 100 nM) elicited by submaximal concentrations of AII; in contrast, DA did not attenuate either basal or adrenocorticotropic hormone-stimulated cell activity. The pharmacological characterization of DA effects with dopaminergic agonists and antagonists strongly indicated an involvement of D-2 receptors. Indeed, selective D-2 agonists were more effective than DA in inhibiting the glomerulosa cell responses to AII; in addition, the effects of DA on both aldosterone secretion and cAMP formation were prevented by D-2 antagonists, such as (-)-sulpiride and domperidone, but not by the selective D-1 antagonist SCH 23390. These data suggest a specific functional interaction between D-2 receptors apparently associated with inhibition of cAMP formation and AII in the regulation of aldosterone production.

Adrenal Cortex↗
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

Reversal by the selective D-2 dopamine receptor blocker sulpiride of the hypotensive effect of co-dergocrine in elderly hypertensives.

The aim of the study was to define the role of peripheral dopaminergic mechanisms in the regulation of blood pressure. The data suggest that the hypotensive effect of the dopaminergic agonist co-dergocrine in elderly hypertensive patients is mediated by interaction with peripheral DA-2 receptors, since it was reversed by the selective antagonist sulpiride in a dose that does not significantly cross the blood brain barrier. The findings suggest the possible therapeutic use of dopamine DA-2 agonists in elderly hypertensive patients.

Aged↗
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

Effect of lead exposure on dopaminergic receptors in rat striatum and nucleus accumbens.

Haloperidol- and sulpiride-displaceable [3H]spiroperidol binding and the dopamine-inhibited adenylate cyclase were measured in rats chronically exposed to lead acetate. Haloperidol-displaceable [3H]spiroperidol binding was unmodified while sulpiride-displaceable binding was increased in striatum and decreased in nucleus accumbens. In addition, the decrease of sulpiride-displaceable binding in nucleus accumbens was paralleled by a reduced ability of bromocriptine to inhibit cAMP formation in presence of the D1 receptor antagonist SCH 23390. The results support the concept that in vivo lead treatment affects dopaminergic receptors and that the binding sites labelled by [3H]spiroperidol displaced by haloperidol may be different from those which recognize sulpiride.

Adenylyl Cyclases↗
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

Chronic lead exposure alters dopaminergic mechanisms in rat pituitary.

The effect of chronic lead treatment on pituitary dopamine (DA) D2 receptors was studied by measuring (-)sulpiride-displaceable [3H]spiroperidol-binding and DA-inhibited adenylate cyclase. Receptor number was reduced in lead-exposed animals and bromocriptine was less able to inhibit cyclase activity in pituitary homogenates. In addition, the capacity of DA to inhibit the VIP-stimulated cAMP formation was decreased.

Adenylyl Cyclase Inhibitors↗
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↗