Pharmacological evidence for inhibition of acth secretion by a central adrenergic system in the dog

Ganong, William F.; Kramer, Norman J.; Salmon, Jane E.; Reid, Ian A.; Lovinger, Robert D.; Scapagnini, U.; Boryczka, A. T.; Shackelford, Roy

doi:10.1016/0306-4522(76)90073-7

Cited by 78 publications

(36 citation statements)

References 16 publications

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“…Thus, in vivo treatment with Anticort does not affect the basal adrenal function, but rather it controls the stress-induced glucocorticoid levels, thus maintaining lower "normal" circulating corticosterone levels. It should be noted, however, that procaine has been also described to decrease the release of corticotropin-releasing factor previously induced in a model of cerebral hemorrhage in rats (Plotsky and Vale, 1984) and to decrease the release of adrenocorticotropin in a model of surgically induced stress in the dog (Ganong et al, 1976). Such a central effect of procaine on the hypothalamus and pituitary cannot be excluded to explain the decrease of the corticosterone concentrations we observed in the in vivo experiments, in addition to a direct effect on the adrenal cells, reinforcing the interest of procaine and its derivatives as corticosteroid modulating agents.…”

Section: Downloaded Frommentioning

confidence: 99%

Inhibition of Adrenal Cortical Steroid Formation by Procaine Is Mediated by Reduction of the cAMP-Induced 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Messenger Ribonucleic Acid Levels

Xu¹,

Lecanu²,

Han³

et al. 2003

J Pharmacol Exp Ther

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Elevated glucocorticoid levels are associated with many diseases, including age-related depression, hypertension, Alzheimer's disease, and acquired immunodeficiency syndrome. Cortisol-lowering agents could provide useful complementary therapy for these disorders. We examined the effect of procaine and procaine in a pharmaceutical formulation on adrenal cortical steroid formation. Procaine inhibited dibutyryl cyclic AMP (dbcAMP)-induced corticosteroid synthesis by murine Y1 and human H295R adrenal cells in a dose-dependent manner without affecting basal steroid formation. Treatment of rats with the procaine-based formulation reduced circulating corticosterone levels. This steroidogenesis-inhibiting activity of procaine was not observed in Leydig cells, suggesting that the effect was specific to adrenocortical cells. In search of the mechanism underlying this inhibitory effect on cAMP-induced corticosteroidogenesis, procaine was found to affect neither the cAMPdependent protein kinase activity nor key proteins involved in cholesterol transport into mitochondria, cytochrome P450 side chain cleavage enzyme expression, and enzymatic activities associated with cholesterol metabolism to final steroid products. However, procaine reduced in a dose-dependent manner the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoA) activity and the dbcAMP-induced HMG-CoA reductase mRNA levels by affecting mRNA stability. These data suggest that the inhibitory effect of procaine on cAMP-induced corticosteroid formation is due to the reduced synthesis of cholesterol. This modulatory effect of procaine on HMG-CoA reductase mRNA expression was also seen in dbcAMP-stimulated Hepa1-6 mouse liver hepatoma cells. Taken together, these results suggest that procaine may provide a pharmacological means for the control of hormone-induced HMG-CoA reductase mRNA expression and hypercortisolemia.

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Section: Downloaded Frommentioning

confidence: 99%

Inhibition of Adrenal Cortical Steroid Formation by Procaine Is Mediated by Reduction of the cAMP-Induced 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Messenger Ribonucleic Acid Levels

Xu¹,

Lecanu²,

Han³

et al. 2003

J Pharmacol Exp Ther

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“…Other evidence indicates that stimulation of a-adrenergic receptors in the hypothalamus inhibits ACTH secretion. 90 Clonidine also inhibits vasopressin secretion, 91 and other evidence indicates that vasopressin secretion is inhibited by stimulation of central a-adrenergic receptors (Blair, Reid, Keil and Ganong, unpublished observations).…”

Section: Central Nervous System Regulation Of Renin Secretionmentioning

confidence: 99%

“…73 Other evidence indicates that increases in growth hormone secretion are produced by stimulation of a-adrenergic receptors in the hypothalamus. * 9 Clonidine inhibits ACTH secretion, 90 and this action is also blocked by administration of small doses of phenoxybenzamine 78 but not its vehicle in the third ventricle. Other evidence indicates that stimulation of a-adrenergic receptors in the hypothalamus inhibits ACTH secretion.…”

Section: Central Nervous System Regulation Of Renin Secretionmentioning

confidence: 99%

Neuroendocrine components in the regulation of blood pressure and renin secretion.

Ganong¹,

Rudolph²,

Zimmermann³

1979

Hypertension

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“…Catecholaminergic systems and especially the noredrenergic system have long been regarded as inhibitors of the hypotha-lamic-pituitary-adrenal (HPA)' axis (1)(2)(3)(4)(5)(6)(7)(8). However, recent data obtained from experimental animals and humans indicate that the brainstem noradrenergic (i.e., locus coeruleus [LC]) system and the HPA axis are both activated during physical (e.g., surgery, trauma, hemorrhage, and exercise) and emotional (e.g., depression, panic anxiety attacks, bereavement, examinations, and experimentally induced inescapable shock stress) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro.

Calogero¹,

Gallucci²,

Chrousos³

et al. 1988

J. Clin. Invest.

190

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To further our understanding of the functional role of catecholaminergic systems in regulating hypothalamic corticotropinreleasing hormone (CRH) secretion, we assessed the direct effects of a multiplicity of catecholamine agonists and antagonists on hypothalamic CRH secretion. To accomplish this, we used an in vitro rat hypothalamic organ culture system in which CRH secretion from single explants was evaluated by a specific RIA (IR-rCRH). Norepinephrine (NE) stimulated IRrCRH secretion dose dependently, with peak effects in the nanomolar range. The effect of NE was antagonized by the mixed a antagonist phentolamine, the a, antagonist prazosin, and the a2 antagonist yohimbine, but not by the ,B blocker, L-propanolol. Compatible with these data were the findings that the a, agonist phenylephrine and the a2 agonist clonidine both stimulated IR-rCRH secretion in a dose-dependent fashion. On the other hand, whereas the fi agonist, isoproterenol, caused a weak, non-dose-dependent increase in IR-rCRH secretion, this effect could not be antagonized by L-propanolol. Despite pretreatment with serotonin and acetylcholine antagonists, the effect of NE upon IR-rCRH secretion was undiminished, suggesting that NE-induced CRH secretion is not mediated by either neurotransmitter. On the other hand, pretreatment with y-aminobutyric acid (GABA) attenuated NE-induced IR-rCRH secretion. Whereas epinephrine (E) stimulated IR-rCRH secretion, this occurred only at higher concentrations, and was antagonized by phentolamine, but not by L-propanolol. Dopamine (DA) had a weak stimulatory effect that could be antagonized by the DA, receptor antagonist, SCH 23390, but not by phentolamine.We conclude that NE and E stimulate hypothalamic IRrCRH secretion via a, and a2 receptors. The effect of NE upon IR-rCRH secretion is not apparently mediated by serotonergic or cholinergic interneurons, but is modulated by the inhibitory neurotransmitter, GABA. These data support the idea that the central catecholaminergic systems are excitatory rather than inhibitory upon CRH secretion when acting directly at the hypothalamic level.

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Pharmacological evidence for inhibition of acth secretion by a central adrenergic system in the dog

Cited by 78 publications

References 16 publications

Inhibition of Adrenal Cortical Steroid Formation by Procaine Is Mediated by Reduction of the cAMP-Induced 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Messenger Ribonucleic Acid Levels

Inhibition of Adrenal Cortical Steroid Formation by Procaine Is Mediated by Reduction of the cAMP-Induced 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Messenger Ribonucleic Acid Levels

Neuroendocrine components in the regulation of blood pressure and renin secretion.

Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro.

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