Intracerebroventricular injection of dibutyryl cyclic adenosine 3′,5′-monophosphate increases hypothalamic levels of neuropeptide Y

Akabayashi, Akira; Zaia, Cássia Thaïs Bussamra Vieira; Gabriel, Steven M.; Silva, Iván; Cheung, W.K.; Leibowitz, Sarah F.

doi:10.1016/0006-8993(94)91306-4

Cited by 38 publications

(23 citation statements)

References 49 publications

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“…Moreover, a study also indicated that leptin, a potent adipocyte hormone acting on hypothalamus to reduce appetite, could inhibit fasting-stimulated NPY gene expression through the modulation of PKA/ CRE signaling in hypothalamus (50). However, in contrast to our present findings, several in vitro and in vivo studies had shown that NPY gene was activated by forskolin or cAMP analogs (1,35) and that PKA inhibitors could attenuate the stimulatory effect of feeding induced by peptides (ghrelin or (25). Mechanisms underlying this contradictory effect of PKA on NPY gene expression are unknown.…”

Section: Discussioncontrasting

confidence: 55%

“…In the brain, PKA appears to be implicated in the regulation of behavioral sensitization (12,57), conditioned locomotion (54), and reward-related feeding (4) behaviors induced by AMPH treatment. Moreover, PKA is involved in the regulation of NPY-induced feeding behavior (25,48), and several studies demonstrate that NPY gene is regulated by forskolin or cAMP analogs in vivo (1,20) or in vitro (35). Thus one could hypothesize that PKA might involve the regulation of NPY gene expression during AMPH treatment.…”

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confidence: 99%

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Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats

Hsieh¹,

Yang²,

Kuo³

2007

American Journal of Physiology-Endocrinology and Metabolism

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. Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats. Am J Physiol Endocrinol Metab 292: E123-E131, 2007. First published August 8, 2006; doi:10.1152/ajpendo.00195.2006.-Although amphetamine (AMPH)-induced appetite suppression has been attributed to its inhibitory action on neuropeptide Y (NPY), an appetite neurotransmitter abundant in the brain, molecular mechanisms underlying this effect are not well known. This study examined the possible role of protein kinase A (PKA) and cAMP response element-binding protein (CREB) signaling in this anorectic effect, and the results showed that both PKA and CREB mRNA levels in hypothalamus were increased following AMPH treatment, which was relevant to a reduction of NPY mRNA level. To determine whether PKA or CREB was involved in the anorectic response, intracerebroventricular infusions of antisense oligonucleotide (or missense control) were performed 60 min before daily AMPH treatment in conscious rats, and results showed that either PKA or CREB knockdown could block AMPH-induced anorexia as well as restore NPY mRNA level, indicating the respective involvement of PKA and CREB signaling in the regulation of NPY gene expression. It is suggested that hypothalamic PKA and CREB signaling may involve the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression. amphetamine; neuropeptide Y; feeding behavior; signaling transduction AMPHETAMINE (AMPH) is a well-known appetite suppressant. After the approval in the 1940s and 1950s of AMPH and AMPH-like compounds for the treatment of obesity, AMPH has served as a prototype for the development of subsequent anorectic drugs such as phentermine and phenylpropanolamine (11,38). AMPH derivatives, such as 3,4-methylenedioxymethamphetamine (MDMA, Adam), have emerged over the last two decades as common recreational psychostimulants or "club drugs" because of their hallucinogenic effect with relatively low toxicity (51). In humans, AMPH can be used to treat attention-deficit/hyperactivity disorder (ADHD) because of its psychomotor effects, such as increased attention, restlessness, and feelings of confidence (5, 6). Because of these effects of AMPH, the mechanisms behind AMPH-induced anorexia, weight loss, and psychomotor effects have been investigated extensively.AMPH is regarded as an indirect dopamine agonist. The anorectic action of AMPH is relevant to the central release of biogenic amines (33, 53) that in turn may lead to an inhibitory action on hypothalamic neuropeptide Y (NPY) (28). Acute treatment with AMPH markedly decreases food intake, followed by a gradual return of normal food intake with subsequent daily treatment (27,30,46). NPY, an orexigenic neurotransmitter in the brain, appears to play an essential role in the regulation of feeding behavior (7, 61) and is postulated to control the energy balance by stimulating feeding behavior and inhibiting th...

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Section: Discussioncontrasting

confidence: 55%

mentioning

confidence: 99%

Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats

Hsieh¹,

Yang²,

Kuo³

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…With peripheral injections of 2-deoxy-D-glucose (2-DG), Akabayashi et al (231) have provided evidence showing inhibition of glucose utilization to stimulate the release of CORT and subsequently enhance NPY synthesis in the ARC. A similar response can also be detected after central administration of dibutyryl CAMP, which together with the 2-DG results may reflect the normal, inverse relation between endogenous CAMP and cellular glucose utilization (232). These metabolic processes, linked to precise endocrine and neurochemical changes, appear to have specific behavioral consequences, as indicated by the finding that blockade of glucose utilization preferentially enhances the consumption of carbohydrate (125,126).…”

Section: Interactions Between Cort Insulin and Hypothalamic Neurochesupporting

confidence: 63%

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

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194

127

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The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

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“…In addition, we mapped the expression of PDE3B in the mouse central nervous system through in situ hybridization. Of particular interest is the expression of PDE3B in the arcuate nucleus and lateral hypothalamus (data not shown), where cAMP may play a role in appetite control (27,28). Currently, we are investigating the potential functional roles of PDE3B in mediating leptin-regulated food intake.…”

Section: Discussionmentioning

confidence: 99%

Leptin inhibits insulin secretion by activation of phosphodiesterase 3B.

Zhao¹,

Bornfeldt²,

Beavo³

1998

J. Clin. Invest.

225

170

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Intracerebroventricular injection of dibutyryl cyclic adenosine 3′,5′-monophosphate increases hypothalamic levels of neuropeptide Y

Cited by 38 publications

References 49 publications

Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats

Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Leptin inhibits insulin secretion by activation of phosphodiesterase 3B.

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