Centrally administered adrenomedullin 5 activates oxytocin-secreting neurons in the hypothalamus and elevates plasma oxytocin level in rats

Otsubo, Hiroki; Hyodo, Susumu; Hashimoto, Hirofumi; Kawasaki, Makoto; Suzuki, Hitoshi; Saito, Takeshi; Ohbuchi, Toyoaki; Yokoyama, T.; Fujihara, Hiroaki; Matsumoto, Tetsuro; Takei, Yoshiyuki; Ueta, Yoichi

doi:10.1677/joe-09-0009

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…28 However, there have been no reports of the effects of systemic administration of AM-5 on the secretion of any hormones. The results from this study demonstrate for the first time that, similar to the infusion of AM and AM-2, infusion of AM-5 results in the stimulation of PRA.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-5 in Normal Conscious Sheep

Charles

Rademaker

Richards

2011

Journal of Cardiovascular Pharmacology

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Although blood pressure effects have been reported for adrenomedullin 5 (AM-5), a newly identified member of the calcitonin gene-related peptide superfamily, little is known about other biological actions. We report the integrated hemodynamic, hormonal, and renal actions of AM-5 (10 and 100 ng·kg·min each for 90 minutes) in normal conscious sheep. AM-5 reduced the mean arterial pressure by 12 mm Hg at the end of the high dose (P < 0.001) in association with dose-dependent increments in the heart rate (40 beats/min--high dose, P < 0.001) and cardiac output (50%-high dose, P < 0.001) and dose-dependent falls in calculated total peripheral resistance (P < 0.001). Plasma renin activity (4-fold increment, P < 0.001), aldosterone (2-fold increment, P = 0.014), and cyclic adenosine monophosphate (50% increment, P < 0.001) all rose in response to high dose AM-5. Urine volume and sodium excretion were unchanged. In conclusion, it is observed that intravenous infusions of AM-5 administered to normal conscious sheep induced significant hemodynamic actions including reduced mean arterial pressure and calculated total peripheral resistance and increased heart rate and cardiac output. Concurrently, AM-5 activated plasma cyclic adenosine monophosphate, plasma renin activity, and aldosterone. These actions are similar to those previously reported for AM and AM-2. Thus, AM-5 may be an another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease.

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Section: Discussionmentioning

confidence: 99%

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-5 in Normal Conscious Sheep

Charles

Rademaker

Richards

2011

Journal of Cardiovascular Pharmacology

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“…In addition, OXT cells express the receptor for leptin and administration of leptin at doses that support hypophagia activates OXT neurones . Anorexigenic glucagon‐like peptide‐1 and adrenomedullin increase OXT neuronal activity and/or promote neurohypophyseal release of OXT . Another anorexigenic signal, alpha‐melanocyte stimulating hormone (alpha‐MSH), an endogenous melanocortin 3/4 receptor (MC3/4R) agonist, also stimulates the release of OXT from hypothalamic dendrites and activates c‐Fos in PVN OXT neurones .…”

Section: Oxytocin and Short‐term Control Of Food Intake: Key Findingsmentioning

confidence: 99%

The role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis

Lawson

Olszewski

Weller

et al. 2019

J Neuroendocrinology

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Obesity and its associated complications have reached epidemic proportions in the USA and also worldwide, highlighting the need for new and more effective treatments. Although the neuropeptide oxytocin (OXT) is well recognised for its peripheral effects on reproductive behaviour, the release of OXT from somatodendrites and axonal terminals within the central nervous system (CNS) is also implicated in the control of energy balance. In this review, we summarise historical data highlighting the effects of exogenous OXT as a short‐term regulator of food intake in a context‐specific manner and the receptor populations that may mediate these effects. We also describe what is known about the physiological role of endogenous OXT in the control of energy balance and whether serum and brain levels of OXT relate to obesity on a consistent basis across animal models and humans with obesity. We describe recent data on the effectiveness of chronic CNS administration of OXT to decrease food intake and weight gain or to elicit weight loss in diet‐induced obese (DIO) and genetically obese mice and rats. Of clinical importance is the finding that chronic central and peripheral OXT treatments both evoke weight loss in obese animal models with impaired leptin signalling at doses that are not associated with visceral illness, tachyphylaxis or adverse cardiovascular effects. Moreover, these results have been largely recapitulated following chronic s.c. or intranasal treatment in DIO non‐human primates (rhesus monkeys) and obese humans, respectively. We also identify plausible mechanisms that contribute to the effects of OXT on body weight and glucose homeostasis in rodents, non‐human primates and humans. We conclude by describing the ongoing challenges that remain before OXT‐based therapeutics can be used as a long‐term strategy to treat obesity in humans.

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“…For example, GLP‐1 and melanocortins bind to their respective receptors present on oxytocin cells and directly stimulate oxytocin neuronal activity precipitating the termination of consummatory behaviour . Adrenomedullin‐2 and ‐5, which decrease food intake, also increase the proportion of Fos positive oxytocin neurones and peripheral levels of the hormone ; similarly, leptin administration at doses that decrease appetite engages hypothalamic oxytocin cells expressing the leptin receptor . Conversely, orexigens (e.g.…”

Section: Oxytocin As An Anorexigen: Fundamental Evidencementioning

confidence: 99%

Oxytocin: A Conditional Anorexigen whose Effects on Appetite Depend on the Physiological, Behavioural and Social Contexts

Olszewski

Klockars

Levine

2016

J Neuroendocrinology

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Central oxytocin suppresses appetite. Neuronal activity and the release of oxytocin coincide with satiation, as well as with adverse events (e.g. hyperosmolality, toxicity or excessive stomach distension) that necessitate an immediate termination of eating behaviour. Oxytocin also decreases consumption driven by reward, especially as derived from ingesting carbohydrates and sweet tastants. This review summarises current knowledge of the role of oxytocin in food intake regulation and highlights a growing body of evidence showing that oxytocin is a conditional anorexigen [i.e. its effects on appetite differ significantly with respect to certain (patho)physiological, behavioural and social contexts].

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Centrally administered adrenomedullin 5 activates oxytocin-secreting neurons in the hypothalamus and elevates plasma oxytocin level in rats

Cited by 11 publications

References 53 publications

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-5 in Normal Conscious Sheep

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-5 in Normal Conscious Sheep

The role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis

Oxytocin: A Conditional Anorexigen whose Effects on Appetite Depend on the Physiological, Behavioural and Social Contexts

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