Fragments of pituitary adenylate cyclase activating polypeptide discriminate between type I and II recombinant receptors

Gourlet, Philippe; Vandermeers, André; Vandermeers‐Piret, Marie‐Claire; Rathé, Jean; Neef, Philippe De; Robberecht, Patrick

doi:10.1016/0014-2999(95)00467-5

Cited by 72 publications

(43 citation statements)

References 20 publications

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“…For studies involving antagonism of PACAP receptors, rats were bilaterally pretreated with saline, PACAP(6 -38) (500 pmol/0.25 l per side, Anaspec) or VIP(6 -28) (500 pmol/0.25 l per side, Bachem). PACAP(6 -38) is a widely used PAC1R antagonist; however, it also has antagonistic properties at the VPAC2R (19,27,40,52), and VIP(6 -28) is reported to be a potent nonselective VPAC receptor antagonist (16,38,54) shown to be effective in the hypothalamus (28). Five minutes later, rats received a second bilateral injection of either saline or 50 pmol PACAP followed by subsequent physiological and behavioral measurements.…”

Section: Methodsmentioning

confidence: 99%

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: Methodsmentioning

confidence: 99%

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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show abstract

“…Binding assays show that PACAP acts predominately at the PACAP-specific PAC 1 receptor (Gourlet et al, 1995), but also binds at the VPAC receptors, which recognize a related peptide, vasoactive intestinal peptide (VIP). In mammals it is likely that PACAP exerts many of its effects through the PAC 1 receptor, demonstrated by the striking phenotypic similarities between PACAP-and PAC 1 -knock-out mice (Hashimoto et al, 2000) but not VPAC 1 -or VPAC 2 -knock-out mice (Hughes et al, 2004;Bechtold et al, 2008).…”

Section: Pacap Induces Hypophagia and Thermogenesis Via Pac 1 Receptorsmentioning

confidence: 99%

PACAP Neurons in the Hypothalamic Ventromedial Nucleus Are Targets of Central Leptin Signaling

Hawke

Ivanov²,

Bechtold³

et al. 2009

J. Neurosci.

140

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“…PAC 1 , or PACAPselective receptors, bind both active forms of PACAP, PACAP-27 and PACAP-38, with equally high affinities but bind VIP with much lower affinity (26), whereas nonselective VPAC (VPAC 1 and VPAC 2 ) receptors recognize PACAP-27, PACAP-38, and VIP with similar high affinities (27)(28)(29)(30)(31)(32)(33). At least seven isoforms of the PAC 1 receptor exist due to alternative splicing of the mRNA, whereas no splice variants of VPAC 1 or VPAC 2 are presently known to exist.…”

mentioning

confidence: 99%

VPAC Receptor Modulation of Neuroexcitability in Intracardiac Neurons

DeHaven

Cuevas

2004

Journal of Biological Chemistry

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) have been found within mammalian intracardiac ganglia, but the cellular effects of these neuropeptides remain poorly understood. Fluorometric calcium imaging and whole cell patch clamp recordings were used to examine the effects of PACAP and VIP on [ Pituitary adenylate cyclase-activating polypeptide (PACAP) 1 and vasoactive intestinal polypeptide (VIP) are pleiotropic neuropeptides that belong to the glucagon/secretin/growth hormone-releasing factor family of peptides (1-4). These neuropeptides have pronounced effects on the central nervous system as well as on neurons and effector targets of the autonomic nervous system. For example, in the central nervous system, PACAP is involved in hippocampal synaptic plasticity and associative learning in mice (5), whereas VIP has been shown to regulate intrathalamic rhythm activity and may modulate information transfer through the thalamocortical circuit (6). In the peripheral nervous system, PACAP and VIP appear to play a major role in autonomic regulation of the cardiovascular system. VIP has been shown to cause positive chronotropic and inotropic effects (7-9). In contrast, PACAP has been shown to cause a transient increase in sinus rate and atrial contractility that is followed by negative chronotropic and inotropic responses in isolated canine atria (10). Also, both PACAP and VIP are potent dilators of coronary arteries (11,12). Whereas these neuropeptides can directly influence cardiac tissues, the effects of PACAP and VIP on the heart are in part due to neuroregulatory effects on parasympathetic intracardiac ganglia (9,10,13,14).Mammalian intracardiac ganglia play a major role in neuronal control of the heart and are believed to be capable of independently monitoring and influencing cardiac function. A variety of neurotransmitters and neuromodulators, including PACAP and VIP, appear to be involved in the relaying of information within intracardiac ganglia and onto effector targets such as cardiac valves, coronary arteries, and cardiomyocytes. PACAP and VIP have been detected by immunocytochemistry in nerve fibers in the heart, coronary vasculature, and cardiac parasympathetic ganglia (15)(16)(17)(18)(19)(20). Although extrinsic fibers may be one source of these neuropeptides in the heart (21), PACAP and VIP are also found in cell bodies and nerve fibers of intrinsic cardiac neurons (15)(16)(17)(18)(19)(20). Despite the fact that data clearly demonstrate that these endogenous neuropeptides are potent regulators of the cardiovascular system, the cellular mechanisms mediating their effects remain poorly understood. There are also conflicting reports in the literature concerning the mechanisms by which PACAP and VIP regulate the function of intrinsic cardiac neurons. For example, it has been suggested that PACAP and VIP modulate neurotransmission

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Fragments of pituitary adenylate cyclase activating polypeptide discriminate between type I and II recombinant receptors

Cited by 72 publications

References 20 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

PACAP Neurons in the Hypothalamic Ventromedial Nucleus Are Targets of Central Leptin Signaling

VPAC Receptor Modulation of Neuroexcitability in Intracardiac Neurons

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