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Pituitary adenylate cylase-activating polypeptide receptor: Multiple signaling pathways involved in energy homeostasis

Maunze B (2022) Pituitary adenylate cylase-activating polypeptide receptor: Multiple signaling pathways involved in energy homeostasis. Marquette University Dissertations 1212. Thesis.

Objective: To determine the endogenous role of pituitary adenylate cyclase activating polypeptide (PACAP) in affecting the ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the Type I PAC1 receptor (PAC1R).

Summary: VMN cells expressing PAC1 receptors in Male Sprague Dawley rats were knocked down via injection of Saporin or PACAP-SAP and trafficking also pharmacologically inhibited. This increased meal sizes, reduced total number of meals, and induced body weight gain. PACAP signaling replicates the effects of leptin administration in the VMN and appears to enable leptin regulation of energy homeostasis. Co-immunoprecipitation was used to show that VMN PAC1 and leptin receptors are found in the same cell, and they form an immunocomplex. Inhibiting downstream effectors of PACAP signaling, such as PKA and PKC, enhanced or prevented leptin signaling respectively. The current findings revealed that endogenous PACAP signaling in the VMN has a potent regulatory influence over both energy intake in the form of feeding, and energy output via thermogenesis and locomotor activity. Moreover, PACAP actions in the VMN share nearly identical secondary effects as with leptin administration in the same brain region suggesting that these two neuropeptides could functionally intersect.

Related Products: PACAP-SAP (Cat. #IT-84)

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