Long-term orexigenic effects of AgRP-(83—132) involve mechanisms other than melanocortin receptor blockade

Hagan, Mary M.; Rushing, Paul A.; Pritchard, Laurel M.; Schwartz, Michael W.; Strack, Alison M.; Ploeg, Lex H.T. Van der; Woods, Stephen C.; Seeley, Randy J.

doi:10.1152/ajpregu.2000.279.1.r47

Cited by 258 publications

(192 citation statements)

References 46 publications

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“…However, there may also be significant differences in the mechanisms by which PG932 and other antagonists affect homeostasis. For example, it is known that central administration of a single picomole dose of AgRP, and SHU9119, increase food intake for up to seven days, possibly due to long term alterations in the activity of neurons involved in reward and satiety [16,17]. AgRP is also an inverse agonist at the Mc4r, and it not known whether PG932 has inverse agonist activity [18,31].…”

Section: Discussionmentioning

confidence: 99%

A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally

Sutton

Babin

et al. 2008

Peptides

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Melanocortin receptors are considered promising candidates for the treatment of behavioral and metabolic disorders ranging from obesity to anorexia and cachexia. These experiments examined the response of mice to peripheral injections of two compounds. PG932 is a derivative of SHU9119 which is non-selective antagonist of melanocortin-3 and melanocortin-4 receptors (Mc3r, Mc4r). PG946 is a derivative of a hybrid of alpha-and beta-MSH, and is a moderately selective Mc3r antagonist. SHU9119 increases food intake when administered intracerebroventricularly but is without effect when injected into the periphery. In contrast, PG932 was found to be highly effective at stimulating food intake when administered peripherally by intraperitoneal injection. The orexigenic effect of PG932 required functional Mc4r, suggesting that inhibition of this receptor is involved in the stimulation of food intake. PG946 did not significantly affect on feeding behavior. PG932 is thus a useful new compound for studies examining the regulation of appetite and energy balance, and may also prove useful for the treatment of cachectic conditions.

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Section: Discussionmentioning

confidence: 99%

A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally

Sutton

Babin

et al. 2008

Peptides

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“…AgRP gene expression increases with food deprivation in the arcuate nucleus of laboratory rats and of Siberian hamsters (Hahn et al 1998;Mercer et al 2000) as noted above. In addition, third ventricular, PVH or dorsomedial hypothalamic nucleus injections of AgRP in rats profoundly stimulates food intake, doing so for several days (Hagan et al 2000;Kim et al 2000;Wirth & Giraudo 2000). Previous studies also indicate that the ghrelin-induced increases in food intake in rats are mediated by the melanocortin 3 and 4 receptors (MC-3/4Rs; Kamegai et al 2000Kamegai et al , 2001Nakazato et al 2001).…”

Section: Central Factorsmentioning

confidence: 99%

Physiological mechanisms for food-hoarding motivation in animals

Keen-Rhinehart

Dailey

Bartness

2010

Phil. Trans. R. Soc. B

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The study of ingestive behaviour has an extensive history, starting as early as 1918 when Wallace Craig, an animal behaviourist, coined the terms 'appetitive' and 'consummatory' for the two-part sequence of eating, drinking and sexual behaviours. Since then, most ingestive behaviour research has focused on the neuroendocrine control of food ingestion (consummatory behaviour). The quantity of food eaten, however, is also influenced by the drive both to acquire and to store food (appetitive behaviour). For example, hamster species have a natural proclivity to hoard food and preferentially alter appetitive ingestive behaviours in response to environmental changes and/or metabolic hormones and neuropeptides, whereas other species would instead primarily increase their food intake. Therefore, with the strong appetitive component to their ingestive behaviour that is relatively separate from their consummatory behaviour, they seem an ideal model for elucidating the neuroendocrine mechanisms underlying the control of food hoarding and foraging. This review focuses on the appetitive side of ingestive behaviour, in particular food hoarding, attempting to integrate what is known about the neuroendocrine mechanisms regulating this relatively poorly studied behaviour. An hypothesis is formed stating that the direction of 'energy flux' is a unifying factor for the control of food hoarding.

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“…Consistent with this perspective: (i) leptin receptors are expressed on arcuate hypothalamic neurons that also express POMC or AgRP, (ii) leptin treatment increases expression of POMC mRNA and decreases AgRP mRNA, and (iii) the synthetic melanocortin 3/4 receptor (MC3/4-R) antagonist, SHU-9119, reverses the short-term intake inhibition that follows icv application of leptin (123,164,201). Direct agonist stimulation of MC3/4-R via icv treatment produces a short-latency, dose-related inhibition of food intake that lasts for 24 h, while antagonist treatment yields a robust hyperphagia that persists for several days after a single application (70,83).…”

Section: Melancortinmentioning

confidence: 99%

The Neuroanatomical Axis for Control of Energy Balance

Grill

Kaplan

2002

Frontiers in Neuroendocrinology

351

219

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The hypothalamic feeding-center model, articulated in the 1950s, held that the hypothalamus contains the interoceptors sensitive to blood-borne correlates of available or stored fuels as well as the integrative substrates that process metabolic and visceral afferent signals and issue commands to brainstem mechanisms for the production of ingestive behavior. A number of findings reviewed here, however, indicate that sensory and integrative functions are distributed across a central control axis that includes critical substrates in the basal forebrain as well as in the caudal brainstem. First, the interoceptors relevant to energy balance are distributed more widely than had been previously thought, with a prominent brainstem complement of leptin and insulin receptors, glucose-sensing mechanisms, and neuropeptide mediators. The physiological relevance of this multiple representation is suggested by the demonstration that similar behavioral effects can be obtained independently by stimulation of respective forebrain and brainstem subpopulations of the same receptor types (e.g., leptin, CRH, and melanocortin). The classical hypothalamic model is also challenged by the integrative achievements of the chronically maintained, supracollicular decerebrate rat. Decerebrate and neurologically intact rats show similar discriminative responses to taste stimuli and are similarly sensitive to intake-inhibitory feedback from the gut. Thus, the caudal brainstem, in neural isolation from forebrain influence, is sufficient to mediate ingestive responses to a range of visceral afferent signals. The decerebrate rat, however, does not show a hyperphagic response to food deprivation, suggesting that interactions between forebrain and brainstem are necessary for the behavioral response to systemic/ metabolic correlates of deprivation in the neurologically intact rat. At the same time, however, there is evidence suggesting that hypothalamic-neuroendocrine responses to fasting depend on pathways ascending from brainstem. Results reviewed are consistent with a distributionist (as opposed to hierarchical) model for the control of energy balance that emphasizes: (i) control mechanisms endemic to hypothalamus and brainstem that drive their unique effector systems on the basis of local interoceptive, and in the brainstem case, visceral, afferent inputs and (ii) a set of uni-and bidirectional interactions that coordinate adaptive neuroendocrine, autonomic, and behavioral responses to changes in metabolic status. KEY WORDS: feeding behavior; leptin; glucose sensing; decerebrate; neuropeptide; hypothalamic model; caudal brainstem; energy balance.

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Long-term orexigenic effects of AgRP-(83—132) involve mechanisms other than melanocortin receptor blockade

Cited by 258 publications

References 46 publications

A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally

A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally

Physiological mechanisms for food-hoarding motivation in animals

The Neuroanatomical Axis for Control of Energy Balance

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