Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus

Hannibal, Jens; Mikkelsen, Jens D.; Clausen, Helle V.; Holst, Jens J.; Wulff, Birgitte S.; Fahrenkrug, Jan

doi:10.1016/0167-0115(94)00099-j

Cited by 180 publications

(159 citation statements)

References 25 publications

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“…Expression of multiple PACAP receptor subtypes in the hypothalamus suggests that PACAP is a multifunctional neuropeptide signal that contributes to several behavioral and physiological systems. The feasibility of this concept is supported by reports linking PACAP to stress (51), anxiety (22), feeding (27,40,50), and glucose mobilization (60), all systems that may work synergistically and converge on PACAP-enriched anatomic areas such as the hypothalamus and amygdala (25).…”

Section: Discussionmentioning

confidence: 66%

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Resch

Maunze

Gerhardt

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Resch JM, Maunze B, Gerhardt AK, Magnuson SK, Phillips KA, Choi S. Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism. Am J Physiol Endocrinol Metab 305: E1452-E1463, 2013. First published October 22, 2013; doi:10.1152/ajpendo.00293.2013.-Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei, suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites; however, meal pattern analysis revealed that only injections into the PVN produced significant reductions in meal size, duration, and total time spent eating. PACAP-mediated hypophagia in both the PVN and VMN was abolished by PAC1R antagonism, whereas pretreatment with a VPACR antagonist had no effect. PACAP injections into the VMN produced unique changes in metabolic parameters, including significant increases in core body temperature and spontaneous locomotor activity that was PAC1R dependent whereas, PVN injections of PACAP had no effect. Finally, PACAP-containing afferents were identified using the neuronal tracer cholera toxin subunit B (CTB) injected unilaterally into the PVN or VMN. CTB signal from PVN injections was colocalized with PACAP mRNA in the medial anterior bed nucleus of the stria terminalis, VMN, and lateral parabrachial nucleus (LPB), whereas CTB signal from VMN injections was highly colocalized with PACAP mRNA in the medial amygdala and LPB. These brain regions are known to influence energy homeostasis perhaps, in part, through PACAP projections to the PVN and VMN.feeding; activity; temperature; hypothalamus; rat PITUITARY ADENYLATE CYCLASE-ACTIVATING polypeptide (PACAP) is a key regulator of several hypothalamic systems, including stress (1), osmoregulation (17), thermoregulation (21), and body weight (27). PACAP was first discovered to influence energy homeostasis through inhibition of feeding in mice following a single intracerebroventricular (icv) injection of the peptide (39). These results combined with reports of dietspecific alterations of PACAP mRNA expression in the hypothalamic ventromedial nuclei (VMN) suggest that PACAP is responsive to nutritional status and directly tied to metabolic systems linked to energy expenditure (27,40). In addition to reducing food intake, icv administration of PACAP modulates autonomic nerve activity (55) as well as hepatic glucose production (60). As a ligand, PACAP binds to three different G protein-coupled receptors, the PAC1 receptor (PAC1R), and the receptors originally discovered as targets...

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Section: Discussionmentioning

confidence: 66%

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Resch

Maunze

Gerhardt

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…PACAP and its receptors are actively expressed in the hypothalamus, which plays a pivotal role in the control of appetite and energy homeostasis (Masuo et al, 1993;Usdin et al, 1994;Hannibal et al, 1995;Sheward et al, 1995;Piggins et al, 1996;Shioda et al, 1997). In fact, it has been previously shown that intracerebroventricular (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

Mounien

Rego

Bizet

et al. 2008

Neuropsychopharmacol

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and the proopiomelanocortin (POMC)-derived peptide, a-melanocytestimulating hormone (a-MSH), exert anorexigenic activities. While a-MSH is known to inhibit food intake and stimulate catabolism via activation of the central melanocortin-receptor MC4-R, little is known regarding the mechanism by which PACAP inhibits food consumption. We have recently found that, in the arcuate nucleus of the hypothalamus, a high proportion of POMC neurons express PACAP receptors. This observation led us to investigate whether PACAP may inhibit food intake through a POMC-dependent mechanism. In mice deprived of food for 18 h, intracerebroventricular administration of PACAP significantly reduced food intake after 30 min, and this effect was reversed by the PACAP antagonist PACAP6-38. In contrast, vasoactive intestinal polypeptide did not affect feeding behavior. Pretreatment with the MC3-R/MC4-R antagonist SHU9119 significantly reduced the effect of PACAP on food consumption. Central administration of PACAP induced c-Fos mRNA expression and increased the proportion of POMC neuronexpressing c-Fos mRNA in the arcuate nucleus. Furthermore, PACAP provoked an increase in POMC and MC4-R mRNA expression in the hypothalamus, while MC3-R mRNA level was not affected. POMC mRNA level in the arcuate nucleus of PACAP-specific receptor (PAC1-R) knock-out mice was reduced as compared with wild-type animals. Finally, i.c.v. injection of PACAP provoked a significant increase in plasma glucose level. Altogether, these results indicate that PACAP, acting through PAC1-R, may inhibit food intake via a melanocortin-dependent pathway. These data also suggest a central action of PACAP in the control of glucose metabolism.

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“…PACAP-38 is the predominant peptide and represents more than 90% of the total PACAP content in most tissues, including the CNS. [13][14][15][16] PACAP has been identified in human sensory 17 and parasympathetic 4 ganglia, as well as in second-order neurons of the trigeminal nucleus caudalis (TNC). 18 The N-terminal 28 amino acids of PACAP-38 share 68% homology with VIP, 19 and the two related peptides are colocalized in rat parasympathetic ganglia.…”

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confidence: 99%

The PACAP Receptor: A Novel Target for Migraine Treatment

2010

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Summary:The origin of migraine pain has not yet been clarified, but accumulating data point to neuropeptides present in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in sensory trigeminal neurons and may modulate nociception at different levels of the nervous system. Human experimental studies have shown that PACAP-38 infusion induces marked dilatation of extracerebral vessels and delayed migraine-like attacks in migraine patients. PACAP selectively activates the PAC 1 receptor, which suggests a possible signaling pathway implicated in migraine pain. This review summarizes the current evidence supporting the involvement of PACAP in migraine pathophysiology and the PAC 1 receptor as a possible novel target for migraine treatment.

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Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus

Cited by 180 publications

References 25 publications

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

The PACAP Receptor: A Novel Target for Migraine Treatment

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