Dopamine during α- or β-Adrenergic Blockade in Man

Lorenzi, Mara; Karam, John H.; Tsalikian, Eva; Bohannon, Nancy J. V.; Gerich, John E.; Forsham, Peter H.

doi:10.1172/jci109304

Cited by 44 publications

(7 citation statements)

References 40 publications

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“…This hemodynamic pattern of dopamine is comparable with that published in the literature (Goldberg 1989;Levinson et al 1985;Lorenzi et al 1979;Os et al 1987;Smit et al 1988;Ensinger et al 1993). While the diastolic blood pressure response to dopamine was nearly identical in the presence and absence of bisoprolol and propranolol both the/71-and the non-selective/?-adrenoceptor antagonist suppressed dopamine induced increases in systolic blood pressure and heart rate to about the same degree indicating that these dopamineeffects are mediated by /?l-adrenoceptor stimulation (Daul et al 1995).…”

Section: Discussionsupporting

confidence: 86%

“…Based on these findings the concept emerged that in humans prolactin release is under dopaminergic control via DA-2 receptors (Ben-Jonathan 1985; Benker et al 1990). The results of this study show that, in healthy male volunteers, infusions of not only dopamine (Levinson et al 1985;Lorenzi et al 1979;Os et al 1987) but also of its N-methyl-derivative, epinine, caused dose-dependent decreases in serum prolactin levels. These effects were unaffected by the/~l-adrenoceptor antagonist bisopropol or the non-selective /Ladrenoceptor antagonist propranolol indicating that /3-adrenoceptors were not involved.…”

Section: Discussionmentioning

confidence: 66%

“…It is well known that activation of pituitary DA-receptors by dopamine causes a decrease in serum prolactin levels (Levinson et al 1985;Lorenzi et al 1979;Os et al 1987); this is not blocked by cz-or /~-adrenoceptor antagonists (Lorenzi et al 1979) indicating that it is a specific dopaminergic effect. On the other hand, DA-2 receptor antagonists such as sulpiride or domperidone significantly increase serum prolactin levels.…”

Section: Discussionmentioning

confidence: 99%

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Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers

Daul

Elter-Schulz

Poller

et al. 1995

Naunyn-Schmiedeberg's Arch Pharmacol

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Epinine (N-methyl-dopamine, the active metabolite of ibopamine), is a full agonist at dopamine (DA)-receptors and alpha- and beta-adrenoceptors. To study whether in vivo DA-receptors mediated effects can be separated from alpha- and beta-adrenoceptor effects we compared in 10 male volunteers the effects of i.v. epinine (0.5; 1; 2; 4 micrograms/kg/min for 15 min each) on DA-receptor (changes in serum prolactin)- and alpha- and beta-adrenoceptor (changes in systolic [Psyst] and diastolic blood pressure [Pdiast] and heart rate)-mediated effects with those of dopamine before and after propranolol (5 mg i.v. 45 min pre-infusion), bisoprolol (15 mg p.o. 2 h pre-infusion) and domperidone (10 mg p.o. 1 h pre-infusion). At the 0.5 and 1 microgram doses of dopamine and epinine did not effect Psyst, Pdiast and heart rate but significantly decreased prolactin levels. At the higher dose both dopamine and epinine significantly increased Psyst and heart rate, while only epinine significantly increased Pdiast. In addition, both dopamine and epinine significantly increased diuresis and natriuresis; in contrast, only dopamine, but not epinine dose-dependently increased plasma noradrenaline levels. Domperidone did not affect dopamine- and epinine-evoked blood pressure- and heart rate-changes, but antagonized their prolactin-effects (at least at the lower doses). Bisoprolol and propranolol significantly reduced dopamine-induced Psyst- and heart rate-increases to about the same extent. Propranolol enhanced epinine-induced Psyst- and Pdiast-increases while bisoprolol reduced epinine-evoked Psyst-increase but not Pdiast-increase. Epinine-induced heart rate-increase was abolished by bisoprolol and was converted into heart rate-decrease by propranolol. We concluded that in 0.5 and 1 microgram doses (plasma levels of 20-80 nmol/l)epinine acts only at DA-receptors. Thus, ibopamine in therapeutically recommended doses (3 x 100 mg/day with peak plasma epinine-levels of 50-80 nmol/l) very likely activates only DA-receptors. In higher doses, however, epinine-like dopamine-activates alpha- and beta-adrenoceptors whereby epinine has a stronger alpha-adrenoceptor agonistic activity than dopamine. Moreover, part of the dopamine-effects are indirect via release of endogenous noradrenaline whereas epinine-effects do not appear to include an indirect component.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers

Daul

Elter-Schulz

Poller

et al. 1995

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Alternatively, by secreting their monoamine content directly into the circulation they might modify the responses of peripheral structures such as pancreatic islets [30]. Dopamine, like other catecholamines, is known to inhibit glucose-induced insulin release from islets of ob/ob mice [31] and to stimulate glucagon secretion [32,33].…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural detection of granulated cells in the autonomic ganglia of the rat pancreas

et al. 1985

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Summary. Electron microscopic examination of the intrinsic autonomic ganglia of the rat pancreas revealed the presence of small cells, when compared to the principal ganglionic neurons, within a particular type of ganglia. The small cells were often located in clusters around fenestrated capillaries, but their most striking characteristic was the presence of catecholamine-like granules distributed throughout the cytoplasm. The possible implication of this new source of catecholamines, acting either as interneurons or as neuroendocrine cells, is discussed in the light of a local regulatory mechanism for islet secretion.Key words: Autonomic nervous system, intrinsic ganglia, small granulated cells, catecholamines, islets of Langerhans, electron microscopy.Certain of the physiologic responses of the endocrine pancreas are mediated by sympathetic discharge via direct stimulation from the central nervous system [1,2]. However, we have recently observed that the glucagon response to glucopenia in the isolated perfused rat pancreas can be largely blocked by phentolamine [3]. Although we concluded that this alpha-adrenergically mediated response to glucopenia must reflect norepinephfine release from severed perinsular sympathetic nerve endings independent of the central nervous system, and since there is no other known source of catecholamines in the pancreas, we undertook a search for an alternative source of catecholamines. In this report we present ultrastructural evidence for a second source of catecholamines based on the demonstration of small cells containing catecholamine-like granules within the intrinsic autonomic ganglia of the rat pancreas. Materials and methodsThree normal albino rats (SiVZ strain, body weight 110 160 g) were used in this study. Under ether anaesthesia the animals were perfused through the left ventricle with 1% glutaraldehyde and 1% paraformaldehyde in 0.1 tool/1 phosphate buffer (pH 7.4) after rinsing of the circulation with 0.9% NaC1 solution. After fixation, small samples of both ventral and dorsal parts of the pancreas were dissected out, postfixed in 2% buffered OsO4, dehydrated and embedded in Epon. Pancreatic ganglia were identified on 1 ~tm thick toluidine blue stained sections. After staining with uranyl acetate and lead citrate, ultrathin sections were viewed in a Philips EM 301 electron microscope. For the quantitative analysis, the volume density of the different components of 8 ganglia (principal neurons, small granulated cells, satellite cells and blood capillaries) was determined on semithin sections using the point-counting method [4]. Data for each component were expressed as % of the total volume density occupied by the 8 ganglia. In the small granulated cells, the size (nm) and density (number/p~m 2) of the vesicles was quantified on electron micrographs at 55 000 magnification, calibrated with a Fullham reference grid, 2160lines/ram (Schenectady, NY, USA). ResultsIn both duodenal and splenic parts of the pancreas (Fig. 1), two types of autonomic ganglia were observed. On...

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“…remains somewhat enigmatic. Various studies with dopamine have shown either no effect on GH release (6)(7)(8) or, more commonly, an augmentation of GH secretion (9)(10)(11). Conversely, dopamine and its agonists have been shown to inhibit GH release in acromegalic subjects (12,13) and inhibit the secretion of GH from normal and acromegalic pituitaries in vitro (14,15), hence the utilization of the dopaminergic drug bromocriptine in the treatment of acromegaly (16,17).…”

mentioning

confidence: 99%

Stimulation of Growth Hormone Release in Man by the Potent D2-Dopamine Agonist CV 205-502: Comparison of Responses to Intravenous and Oral Administration*

Miell

Pralong²,

Corder³

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

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It is well known that dopaminergic agents are stimulators of GH release in man, and although responses are sometimes unreliable, oral L-dopa and iv dopamine have frequently been employed in the evaluation of GH-deficient states. To assess the effects on GH secretion of a new potent D2-dopamine agonist, the octahydrobenzo(g)quinoline CV 205-502 (CV) we have investigated the GH responses in healthy male volunteers to four different iv doses. For this purpose 3 separate groups of 9 subjects were studied. The respective groups were administered on separate occasions 10 micrograms CV and placebo (group 1), 5 micrograms, 2.5 micrograms, and placebo (group 2), and 1 microgram and placebo (group 3). Each subject received drug and placebo in a double blind randomly assigned order, with at least 5 days between their administration. Active compound or placebo was infused over 30 min, and blood sampling was carried out for 72 h after cessation of infusion. Peak GH levels occurred between 45-60 min after the end of the infusion; the observed maximum GH concentrations were 19.2 +/- 2.9 micrograms/L (10 micrograms, iv; P less than 0.001 vs. placebo), 9.61 +/- 2.1 (5 micrograms, iv; P less than 0.001 vs. placebo), 4.7 +/- 1.7 (2.5 micrograms, iv; P less than 0.05 vs. placebo), and 1.9 +/- 0.8 micrograms/L (1 micrograms, iv; P = NS vs. placebo). The mean integrated GH secretion expressed in arbitrary units [area under the response curve (AUC)] up to 3 h postinfusion showed a typical dose-response relationship. Mean values were 1715 +/- 269.4 (10 micrograms, iv; P less than 0.001 vs. placebo), 956.1 +/- 189.9 (5 micrograms, iv; P less than 0.001 vs. placebo), 312.8 +/- 105.8 (2.5 micrograms, iv), and 162.8 +/- 47.5 (1 microgram, iv). In a second study with a separate group of 18 volunteers, we compared the GH response to an oral dose of 100 micrograms CV with those to 5 micrograms CV given iv and placebo treatment. Peak GH values in this study were 20.3 +/- 5.5 micrograms/L (100 micrograms, orally; P less than 0.01 vs. placebo) and 14.6 +/- 2.8 (5 micrograms, iv; P less than 0.001 vs. placebo). Maximum levels occurred 45 min after the infusion and 90 min after ingestion (60 min relative to the end of the infusion).(ABSTRACT TRUNCATED AT 400 WORDS)

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Dopamine during α- or β-Adrenergic Blockade in Man

Cited by 44 publications

References 40 publications

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers

Ultrastructural detection of granulated cells in the autonomic ganglia of the rat pancreas

Stimulation of Growth Hormone Release in Man by the Potent D2-Dopamine Agonist CV 205-502: Comparison of Responses to Intravenous and Oral Administration*

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