Pituitary Adenylate Cyclase-Activating Polypeptide Induces a Sustained Increase in Intracellular Free Ca2+Concentration and Catecholamine Release by Activating Ca2+Influx via Receptor-Stimulated Ca2+Entry, Independent of Store-Operated Ca2+Channels, and Voltage-Dependent Ca2+Channels in Bovine Adrenal Medullary Chromaffin Cells

Morita, Kenichi; Sakakibara, Akira; Kitayama, Shigeo; Kumagai, Kozo; Tanne, Kazuo; Dohi, Toshihiro

doi:10.1124/jpet.102.033456

Cited by 33 publications

(15 citation statements)

References 57 publications

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“…Filipsson et al (26) reported that PACAP has dual functions in regards to glucose homeostasis -PACAP injected intravenously inhibits insulin sensitivity and stimulates insulin secretion with no alteration in net glucose homeostasis. The former could be partly explained by PACAP-induced increase of catecholamine release from adrenal chromaffin cells (27). This possibility was confirmed in Adcyap1 −/ − mice by Hamelink et al (10).…”

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confidence: 63%

Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

et al. 2008

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Abstract. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide implicated in several metabolic functions, including insulin secretion and sympathoadrenal activation. To clarify the roles of PACAP in maintenance of whole-body glucose and lipid homeostasis, the impact of the deletion of PACAP on glucose homeostasis, body weight, and adipose tissue mass was examined by comparing mice lacking the Adcyap1 gene encoding PACAP (Adcyap1) with wild-type littermate controls. Adcyap1 −/− mice showed significant hypoinsulinemia, although being normoglycemic, and lower body weight as well as reduced food intake. They also showed greatly reduced white adipose tissue mass, in which the mRNA expression of adipocyte fatty acid-binding protein (aP2), a marker of adipocyte differentiation, was decreased. Glucose and insulin tolerance tests revealed increased insulin sensitivity in Adcyap1 −/ − mice. In accordance with these observations, plasma levels of resistin, an adipocytokine implicated in insulin resistance, were decreased in Adcyap1 −/ − mice. After a high-fat dietary challenge for six weeks, Adcyap1 −/− mice still showed lower body weights and increased insulin sensitivity. These results indicate the crucial roles of PACAP in energy metabolism, including lipid metabolism, and in the regulation of body weight, raising the possibility that the PACAP-signaling pathway that favors energy storage could be a therapeutic target for obesity.

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confidence: 63%

Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

et al. 2008

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“…It is well established that PACAP increases [Ca 2ϩ ] i by mobilizing intracellular pools or by increasing extracellular calcium influx (Chatterjee et al, 1996;Przywara et al, 1996;Osipenko et al, 2000;Morita et al, 2002;Liu et al, 2003;Payet et al, 2003). Our data favor the notion that in cortical precursors PACAP promotes calcium entry from the extracellular milieu, in agreement with previous reports indicating that PACAPinduced Ca 2ϩ influx requires the activation of cAMP-dependent signaling (Przywara et al, 1996;Osipenko et al, 2000).…”

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confidence: 83%

DREAM Mediates cAMP-Dependent, Ca2+-Induced Stimulation of GFAP Gene Expression and Regulates Cortical Astrogliogenesis

Cebolla¹,

Fernández-Pérez²,

Perea³

et al. 2008

Journal of Neuroscience

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In the developing mouse brain, once the generation of neurons is mostly completed during the prenatal period, precisely coordinated signals act on competent neural precursors to direct their differentiation into astrocytes, which occurs mostly after birth. Among these signals, those provided by neurotrophic cytokines and bone morphogenetic proteins appear to have a key role in triggering the neurogenic to gliogenic switch and in regulating astrocyte numbers. In addition, we have reported previously that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (

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“…PACAP attenuates cardiac baroreceptor reflex sensitivity in trout (34), but this reflex is controlled predominantly by the parasympathetic system. Long-term effects of PACAP have also been seen in sympathetic neurons (33,64), adrenal medullary cells (6,45), and tyrosine hydroxylase phosphorylation (9). We do not believe that the absence of effect on adaptive reflexes is an artifact of the preparation, since many of our earlier studies (1,2,19,50,57) with peptides have demonstrated differential effects on the reflexes studied here.…”

Section: Discussionmentioning

confidence: 99%

PACAP causes PAC₁/VPAC₂ receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats

Farnham

Lung

Tallapragada

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Farnham MM, Lung MS, Tallapragada VJ, Pilowsky PM. PACAP causes PAC 1/VPAC2 receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats. Am J Physiol Heart Circ Physiol 303: H910 -H917, 2012. First published August 10, 2012; doi:10.1152/ajpheart.00464.2012.-Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide that plays an important role in hypertension and stress responses. PACAP acts at three G protein-coupled receptors [PACAP type 1 receptor (PAC 1 ) and vasoactive intestinal peptide receptor types 1 and 2 (VPAC 1 and VPAC2)] and is localized to sites involved in cardiovascular control, most significantly the rostral ventrolateral medulla (RVLM). The RVLM is crucial for the tonic and reflex control of efferent sympathetic activity. Increases in sympathetic activity are observed in most types of hypertension and heart failure. PACAP delivered intrathecally also causes massive sympathoexcitation. We aimed to determine the presence and abundance of the three PACAP receptors in the RVLM, the role, in vivo, of PACAP in the RVLM on tonic and reflex cardiovascular control, and the contribution of PACAP to hypertension in the spontaneously hypertensive rat (SHR). Data were obtained using quantitative PCR and microinjection of PACAP and its antagonist, PACAP(6 -38), into the RVLM of anesthetized artificially ventilated normotensive rats or SHRs. All three receptors were present in the RVLM. PACAP microinjection into the RVLM caused sustained sympathoexcitation and tachycardia with a transient hypertension but did not affect homeostatic reflexes. The responses were partially mediated through PAC1/VPAC2 receptors since the effect of PACAP was attenuated (ϳ50%) by PACAP(6 -38). PACAP was not tonically active in the RVLM in this preparation because PACAP(6 -38) on its own had no inhibitory effect. PACAP has long-lasting cardiovascular effects, but altered PACAP signaling within the RVLM is not a cause of hypertension in the SHR. blood pressure; rostral ventrolateral medulla; sympathetic; neuropeptides; pituitary adenylate cyclase-activating polypeptide; vasoactive intestinal peptide receptor PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) exists in discrete regions of the brain stem and spinal cord involved in cardiovascular control, one of which is the rostral ventrolateral medulla (RVLM) (7,12,17,22,35,59). The RVLM is crucial for cardiovascular control (20,40,48,49) as it contains the neurons that determine resting mean arterial pressure (MAP) and responds to the activation of adaptive reflexes (11,21,37,38,51). Changes in autonomic function resulting from activation of the baroreceptor, somatosympathetic, and chemoreceptor reflexes are all principally mediated by increasing or decreasing the activity of RVLM neurons, which, in turn, project to and excite sympathetic preganglionic neurons in the thoracolumbar spinal cord (28,36,39,43,44,49,62).Peripheral administration of PACAP-38 (PACAP) dilates blood vessels, causing hypotension (42, 53). Centra...

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Cited by 33 publications

References 57 publications

Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

DREAM Mediates cAMP-Dependent, Ca2+-Induced Stimulation of GFAP Gene Expression and Regulates Cortical Astrogliogenesis

PACAP causes PAC₁/VPAC₂ receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats

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Abstract: ABSTRACT

Cited by 33 publications

References 57 publications

Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

DREAM Mediates cAMP-Dependent, Ca2+-Induced Stimulation of GFAP Gene Expression and Regulates Cortical Astrogliogenesis

PACAP causes PAC1/VPAC2 receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats

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PACAP causes PAC₁/VPAC₂ receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats