Search PubMed⌕ Search

Biomedical subjects

P Spano

Publications and source records attributed to P Spano.

67 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

Ontogenesis of alpha- and beta-receptors located on cerebral microvessels.

Adrenergic receptors in rat brain microvessels were studied during ontogenesis. Microvessels were prepared by albumin floatation and glass bead filtration techniques from cortices of 10, 20- and 90-day-old rats. The lower level of alpha 1- alpha 2- and beta-receptor sites observed in early life may correlate with the lower capacity of cerebral vascular regulatory mechanism in this period.

Aging↗

Characterization of beta-adrenergic receptors on human cerebral microvessels.

Cerebral microvessels were separated and prepared from human brain cortex by albumin floatation and glass bead filtration. The binding of a specific beta-adrenergic antagonist, (125I) iodohydroxybenzylpindolol, to the microvessel preparation was characterized by high affinity, saturability, and stereospecificity. The presence of specific beta-adrenergic receptor sites in human cerebral microvessels supports the hypothesis of adrenergic regulation of the function of cerebral microvessels.

Brain↗

Subtypes of beta-adrenergic receptors in rat cerebral microvessels.

The 125I-labeled iodohydroxybenzylpindolol (IHYP) binding to beta-receptors on brain micro-vessels is inhibited by isoproterenol, epinephrine and norepinephrine, with Ki values of 2 X 10(-7) M, 2.5 X 10(-6) M and 1.2 X 10(-5) M, respectively. A modified Scatchard analysis of the inhibitory effects of practolol, metroprolol and zinterol on IHYP binding has shown that the proportion of beta 2-receptors in our preparation is about 80% of the total beta-adrenergic receptor population. Our data indicate that the beta-adrenergic receptors located on cerebral microvessels are of both beta 1 and beta 2 types, with a predominance of the beta 2 type.

Animals↗

Interaction of sulfpride and ergot derivatives on rat brain DOPAC concentration and prolactin secretion in vivo.

Sulpiride, which differs from classical neuroleptics by not producing major extrapyramidal side effects, is a potent antiemetic agent and stimulates prolactin secretion in both laboratory animals and man. In parallel it increases dopamine synthesis in both striatum and nucleus accumbens. Bromocriptine and metergoline are two effective agents in suppressing prolactin release and postulated to stimulate dopamine receptors. The interactions of these two ergot derivatives with sulpiride have been investigated on prolactin release and on striatal and limbic DOPAC accumulation. Bromocriptine at all doses tested was able to suppress the increased in vivo prolactin secretion observed after sulpiride administration. Metergoline antagonized the sulpiride-induced prolactin increase only at low doses; on the contrary higher doses potentiated it. High concentrations of bromocriptine suppressed the sulpiride-induced increased of DOPAC levels in striatum and n. accumbens, while metergoline potentiated the sulpiride-induced accumulation of brain DOPAC.

3,4-Dihydroxyphenylacetic Acid↗

Dopamine D2, D3, and D4 receptor mRNA levels in rat brain and pituitary during aging.

Reverse Transcriptase-Polymerase Chain Reaction technique was used to determine the levels of the mRNAs encoding different receptors belonging to the D2 family in various brain areas of 6-, 12-, 18-, and 24-month-old rats. We found a progressive, age-dependent reduction in the mRNA levels of D2 short and D2 long receptors in corpus striatum, substantia nigra, and frontal cortex. D2 short and D2 long receptor mRNA levels were unchanged in hippocampus and olfactory tubercle, while they increased in pituitary. D3 receptor mRNA levels were reduced in olfactory tubercle and unchanged in striatum. D4 receptor mRNA levels were unmodified in pituitary gland. These data suggest that the molecular mechanisms responsible for regulating the pattern of expression of the various dopamine receptors are differentially regulated by aging.

Aging↗