scholarly journals A Novel Role for Endogenous Pituitary Adenylate Cyclase Activating Polypeptide in the Magnocellular Neuroendocrine System

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 791-803 ◽  
Author(s):  
E. R. Gillard ◽  
M. León-Olea ◽  
S. Mucio-Ramírez ◽  
C. G. Coburn ◽  
E. Sánchez-Islas ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Supraoptic Nucleus ◽  
Potential Role ◽  
Neuroendocrine System ◽  
Neuroendocrine Cells ◽  
Type I ◽  
Pituitary Adenylate Cyclase ◽  
Pacap Receptors ◽  
Magnocellular Neuroendocrine Cells

Central release of vasopressin (VP) by the magnocellular neuroendocrine cells (MNCs) responsible for systemic VP release is believed to be important in modulating the activity of these neurons during dehydration. Central VP release from MNC somata and dendrites is stimulated by both dehydration and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is expressed in MNCs, its potential role in the magnocellular response to dehydration is unexplored. The current study demonstrates that prolonged dehydration increases immunoreactivity for PACAP-27, PACAP-38, and the type I PACAP receptor in the supraoptic nucleus (SON) of the rat. In addition, PACAP stimulates local VP release in the euhydrated rat SON in vitro, and this effect is reduced by the PACAP receptor antagonist PAC6–27 (100 nm), suggesting the participation of PACAP receptors. Concomitant with its effects on local VP release, PACAP also reduces basal glutamate and aspartate release in the euhydrated rat SON. Furthermore, somatodendritic VP release elicited by acute dehydration is blocked by PAC6–27, suggesting that endogenous PACAP participates in this response. Consistent with this, RIA revealed that local PACAP-38 release within the SON is significantly elevated during acute dehydration. These results suggest that prolonged activation of hypothalamic MNCs is accompanied by up-regulation of PACAP and the type I PACAP receptor in these cells and that somatodendritic VP release in response to acute dehydration is mediated by activation of PACAP receptors by endogenous PACAP released within the SON. A potential role for PACAP in promoting efficient, but not exhaustive, systemic release of VP from MNCs during physiological challenge is discussed.

scholarly journals Expression and in vitro regulation of pituitary adenylate cyclase-activating polypeptide (pacap38) and its type I receptor (pac1-r) in the gonads of tilapia (Oreochromis mossambicus)

Reproduction ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 449-467 ◽  
Author(s):  
Wei-Tung Huang ◽  
Chia-Jung Li ◽  
Po-Jui Wu ◽  
Yun-Shiang Chang ◽  
Tai-Lin Lee ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Oreochromis Mossambicus ◽  
Type I ◽  
Dibutyryl Camp ◽  
Pituitary Adenylate Cyclase ◽  
Commercially Important ◽  
And Function ◽  
The Brain ◽  
Cyclase Activator

Pituitary adenylate cyclase-activating polypeptide (PACAP), a pleiotropic neuropeptide, has diverse functions in mammals. However, studies of the expression and function of PACAP and its receptor in fish, particularly in the reproductive system, are still limited. In this report, semi-quantitative RT-PCR and immunohistochemical staining were performed to identify expression domains of commercially important tilapia (Oreochromis mossambicus). PACAP (tpacap38) and its type I receptor (tpac1-r). Transcripts were detected in the brain, gallbladder, gill, heart, intestine, kidney, muscles, pancreas, spleen, stomach, testes, and ovaries, but not in the liver. Expression of tpacap38 and tpac1-r mRNA in brain tissue was significantly higher in both sexes compared with other tissues. Addition of exogenous ovine PACAP38 (0.25–5 nM), cAMP analog (dibutyryl-cAMP, 0.25–1.5 mM) or forskolin (adenylate cyclase activator, 1–10 μM) significantly upregulated tpacap38 in the gonads via a dose- and time-dependent fashion. This effect reached a maximal level at 2 h after induction, and then decreased with prolonged culture for up to 4 or 8 h. Additionally, the expression levels of tpac1-r were not significantly affected by ovine PACAP38 or dibutyryl-cAMP in either sex. Forskolin had a slightly inductive effect and its function could be suppressed with the addition of protein kinase A (PKA) inhibitor, H89 (10 μM), indicating involvement of the cAMP-PKA signaling pathway in the regulation of tpacap38. Expression of tpacap38 and tpac1-r in the gonads of tilapia suggests that PACAP may mediate gonadotropin action via paracrine/autocrine mechanisms in this bony fish.

scholarly journals Signalling Alterations in Bones of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Gene Deficient Mice

2018 ◽  
Vol 19 (9) ◽  
pp. 2538 ◽  
Author(s):  
Gergő Józsa ◽  
Vince Szegeczki ◽  
Andrea Pálfi ◽  
Tamás Kiss ◽  
Zsuzsanna Helyes ◽  
...  
Keyword(s):  
Bone Formation ◽  
Adenylate Cyclase ◽  
Morphological Changes ◽  
Bone Matrix ◽  
Transverse Diameter ◽  
Type I ◽  
Pituitary Adenylate Cyclase ◽  
Deficient Mice

: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with diverse developmental roles, including differentiation of skeletal elements. It is a positive regulatory factor of chondrogenesis and osteogenic differentiation in vitro, but little is known about its in vivo role in bone formation. In our experiments, diaphyses of long bones from hind limbs of PACAP gene-deficient mice showed changes in thickness and increased staining intensity. Our main goal was to perform a detailed morphological and molecular biological analysis of femurs from PACAP knockout (KO) and wild type (WT) mice. Transverse diameter and anterior cortical bone thickness of KO femurs showed significant alterations with disturbed Ca2+ accumulation and collagen type I expression. Higher expression and activity of alkaline phosphatase were also observed, accompanied by increased fragility PACAP KO femurs. Increased expression of the elements of bone morphogenic protein (BMP) and hedgehog signalling was also observed, and are possibly responsible for the compensation mechanism accounting for the slight morphological changes. In summary, our results show that lack of PACAP influences molecular and biomechanical properties of bone matrix, activating various signalling cascade changes in a compensatory fashion. The increased fragility of PACAP KO femur further supports the role of endogenous PACAP in in vivo bone formation.

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylate cyclase and promotes proliferation of mouse primordial germ cells

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 215-221 ◽  
Author(s):  
M. Pesce ◽  
R. Canipari ◽  
G.L. Ferri ◽  
G. Siracusa ◽  
M. De Felici
Keyword(s):  
Adenylate Cyclase ◽  
Germ Cell ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Intracellular Camp ◽  
Type I ◽  
In Vitro Proliferation ◽  
Pituitary Adenylate Cyclase

During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ cells (the embryonic precursors of gametes of the adult animal) proliferate actively. Certain growth factors, such as stem cell factor and leukemia inhibitory factor, seem to be essential for survival, proliferation and possibly differentiation of mouse primordial germ cell in vivo and/or in vitro. Similarly, increase in intracellular cAMP is followed by a marked enhancement of primordial germ cell proliferation, at least in culture. In the present study, we show that pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38), two neuropeptides of the secretin-glucagon-vasoactive intestinal polypeptide-GH-releasing hormone family, stimulate in vitro proliferation of mouse primordial germ cells, bind to primordial germ cells and gonadal somatic cells (possibly to type I PACAP receptor) and activate adenylate cyclase in the same cells. Moreover, PACAP-like immunoreactivity was found in gonadal ridges, mostly on germ cell surface. In conclusion, evidence is provided that PGC proliferation can be stimulated by certain bioactive polypeptides, thus suggesting a novel regulatory role for such compounds in early gonad development.

scholarly journals Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro

2021 ◽  
Vol 11 ◽  
Author(s):  
Tibor Hajdú ◽  
Patrik Kovács ◽  
Emese Zsigrai ◽  
Roland Takács ◽  
Judit Vágó ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
The Body ◽  
Melanoma Progression ◽  
Pituitary Adenylate Cyclase ◽  
Pacap Receptors ◽  
Melanoma Cell Lines

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide which is distributed throughout the body. PACAP influences development of various tissues and exerts protective function during cellular stress and in some tumour formation. No evidence is available on its role in neural crest derived melanocytes and its malignant transformation into melanoma. Expression of PACAP receptors was examined in human skin samples, melanoma lesions and in a primary melanocyte cell culture. A2058 and WM35 melanoma cell lines, representing two different stages of melanoma progression, were used to investigate the effects of PACAP. PAC1 receptor was identified in melanocytes in vivo and in vitro and in melanoma cell lines as well as in melanoma lesions. PACAP administration did not alter viability but decreased proliferation of melanoma cells. With live imaging random motility, average speed, vectorial distance and maximum distance of migration of cells were reduced upon PACAP treatment. PACAP administration did not alter viability but decreased proliferation capacity of melanoma cells. On the other hand, PACAP administration decreased the migration of melanoma cell lines towards fibronectin chemoattractant in the Boyden chamber. Furthermore, the presence of the neuropeptide inhibited the invasion capability of melanoma cell lines in Matrigel chambers. In summary, we provide evidence that PACAP receptors are expressed in melanocytes and in melanoma cells. Our results also prove that various aspects of the cellular motility were inhibited by this neuropeptide. On the basis of these results, we propose PACAP signalling as a possible target in melanoma progression.

Pituitary adenylate cyclase-activating peptide and lung-liquid reabsorption in vitro by lungs from fetal guinea-pigs

2002 ◽  
Vol 80 (11) ◽  
pp. 2000-2005 ◽  
Author(s):  
B Li-Pak-Tong ◽  
S Ram ◽  
A M Perks
Keyword(s):  
Adenylate Cyclase ◽  
Guinea Pigs ◽  
Response Curve ◽  
Neuroendocrine System ◽  
Dilution Method ◽  
Partial Recovery ◽  
Pituitary Adenylate Cyclase ◽  
Lung Liquid ◽  
Liquid Removal

Pituitary adenylate cyclase-activating peptide (PACAP) is present in the lungs, notably in their internal neuroendocrine system; however, its use is not clear. It was investigated for its possible ability to cause lung-liquid reabsorption around birth. Lungs from 31 late-term fetal guinea-pigs (at 60 ± 2 days of gestation) were supported in vitro for 3 h; lung-liquid movements were monitored by a dye-dilution method. Untreated control preparations (n = 9) produced fluid at 1.85 ± 0.40 mL·kg–1 body mass·h–1 (mean ± SD), with no significant change (ANOVA, regression analysis). Those given 10–8 M PACAP in the middle hour turned to reabsorption (n = 3) or reduced production markedly (n = 3) (average fall 84.4 ± 5.4%; significant at P < 0.001–0.0005); effects continued and increased after the PACAP was removed. Preparations given 10–9 M PACAP reacted similarly, but there was partial recovery after treatment (five reabsorbed, four reduced production; average fall 91.4 ± 14.3%; significant at P < 0.01–0.0005). Preparations given 10–10 M PACAP all reduced production, with partial recovery (average fall 43.5 ± 8.2%; significant at P < 0.005–0.0005). Preparations given 10–11 M PACAP showed little or no effect. The linear log dose–response curve became maximal at 10–9 M (r2 = 0.98; theoretical threshold 10–13 M). The results increase the likelihood that the neuroendocrine system is important in lung-liquid reabsorption, and suggest that PACAP could combine its relaxation of airways with lung-liquid removal, and therefore aid the first attempts of the newborn to breathe.

scholarly journals Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish

2000 ◽  
Vol 78 (3) ◽  
pp. 329-343 ◽  
Author(s):  
Anderson OL Wong ◽  
Wen Sheng Li ◽  
Eric KY Lee ◽  
Mei Yee Leung ◽  
Lai Yin Tse ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Adenylate Cyclase ◽  
Protein Kinase A ◽  
Anterior Pituitary ◽  
Kinase C ◽  
Pituitary Adenylate Cyclase ◽  
Pacap Receptors ◽  
Kinase A

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of the secretin-glucagon peptide family. In mammals, this peptide has been located in a wide range of tissues and is involved in a variety of biological functions. In lower vertebrates, especially fish, increasing evidence suggests that PACAP may function as a hypophysiotropic factor regulating pituitary hormone secretion. PACAP has been identified in the brain-pituitary axis of representative fish species. The molecular structure of fish PACAP is highly homologous to mammalian PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is under direct innervation of the hypothalamus and PACAP nerve fibers have been identified in the pars distalis. Using the goldfish as a fish model, mRNA transcripts of PACAP receptors, namely the PAC1 and VPAC1 receptors, have been identified in the pituitary as well as in various brain areas. Consistent with the pituitary expression of PACAP receptors, PACAP analogs are effective in stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of Ca2+ entry through voltage-sensitive Ca2+ channels followed by activation of Ca2+-calmodulin protein kinase II is likely the downstream mechanism mediating PACAP-stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the associated post-receptor signaling events responsible for PACAP-stimulated GTH-II release have not been characterized in goldfish, these findings support the hypothesis that PACAP is produced in the hypothalamus and delivered to the anterior pituitary to regulate GH and GTH-II release in fish.Key words: PACAP, VIP, PAC1 receptor, VPAC1 receptor, VPAC2 receptor, growth hormone, gonadotropin-II, cAMP, protein kinase A, protein kinase C, calcium, pituitary cells, goldfish, and teleost.

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