scholarly journals Microinfusion of Pituitary Adenylate Cyclase-Activating Polypeptide into the Central Nucleus of Amygdala of the Rat Produces a Shift from an Active to Passive Mode of Coping in the Shock-Probe Fear/Defensive Burying Test

2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Gabor Legradi ◽  
Mahasweta Das ◽  
Brian Giunta ◽  
Khemraj Hirani ◽  
E. Alice Mitchell ◽  
...  

High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) nerve fibers are present in the central nucleus of amygdala (CeA), a brain region implicated in the control of fear-related behavior. This study evaluated PACAPergic modulation of fear responses at the CeA in male Sprague-Dawley rats. PACAP (50–100   pmol) microinfusion via intra-CeA cannulae produced increases in immobility and time the rats spent withdrawn into a corner opposite to the electrified probe compared to controls in the shock-probe fear/defensive burying test. Shock-probe burying and exploration, numbers of shocks received, locomotion distance, and velocity were all reduced by intra-CeA PACAP injection. Further, intra-CeA PACAP effects were manifested only when the animals were challenged by shock, as intra-CeA PACAP injections did not cause significant changes in the behaviors of unshocked rats. Thus, intra-CeA administration of PACAP produces a distinct reorganization of stress-coping behaviors from active (burying) to passive modes, such as withdrawal and immobility. These findings are potentially significant toward enhancing our understanding of the involvement of PACAP and the CeA in the neural basis of fear and anxiety.

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 5042-5059 ◽  
Author(s):  
Kong Hung Sze ◽  
Hong Zhou ◽  
Yinhua Yang ◽  
Mulan He ◽  
Yonghua Jiang ◽  
...  

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been proposed to be the ancestral GHRH. Recently, using grass carp as a model for modern-day bony fish, we demonstrated that PACAP nerve fibers are present in close proximity to carp somatotrophs, and mammalian PACAPs can induce GH secretion in carp pituitary cells. To further examine the role of PACAP as a GH-releasing factor in fish, the structural identity of grass carp PACAP was established by molecular cloning. The newly cloned PACAP was found to be a single-copy gene and expressed in the brain but not other tissues. The mature peptides of PACAP, namely PACAP27 and PACAP38, were synthesized. As revealed by nuclear magnetic resonance spectroscopies, carp PACAP38 is composed of a flexible N terminal from His1 to Ile5, an extended central helix from Phe6 to Val26, and a short helical tail in the C terminal from Arg29 to Arg34. The C-terminal helix is located after a hinge region at Leu27 to Gly28 and is absent in the solution structures of PACAP27. The two forms of PACAPs were effective in elevating GH release and GH transcript expression in grass carp pituitary cells. These stimulatory effects occurred with parallel rises in cAMP and Ca2+ entry via voltage-sensitive Ca2+ channels in carp somatotrophs. The present study represents the first report for solution structures of nonmammalian PACAPs and provides evidence that a brain-specific isoform of PACAP in fish can stimulate GH synthesis and release at the pituitary level, presumably by activating the appropriate postreceptor signaling mechanisms.


2012 ◽  
Vol 303 (7) ◽  
pp. R719-R726 ◽  
Author(s):  
Andrea H. Gaede ◽  
Melissa A. Inglott ◽  
Melissa M. J. Farnham ◽  
Paul M. Pilowsky

This study focuses on presympathetic neurons of the rostral ventrolateral medulla (RVLM) that regulate sympathetic vasomotor tone. Many neurotransmitters are colocalized in RVLM neurons and are released under specific conditions to modulate efferent homeostatic responses. Of particular interest here are two peptides colocalized in catecholaminergic RVLM neurons: catestatin and pituitary adenylate cyclase-activating polypeptide (PACAP). Chromogranin A-derived catestatin is a potent endogenous noncompetitive nicotinic and adrenoreceptor antagonist. Catestatin impairs adenylate cyclase and phospholipase C action: mechanisms engaged by PACAP. Although PACAP and catestatin are likely coreleased, the possible effects of this are unknown. We aimed to determine whether catestatin affects the normal sympathoexcitatory but isotensive responses to intrathecal PACAP. Urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats ( n = 22) were given an intrathecal injection of catestatin at different times prior to intrathecal administration of PACAP-38. Arterial pressure, splanchnic sympathetic nerve activity, heart rate, and reflex responses to baroreceptor and chemoreceptor activation were recorded. The key findings of this study are that pretreatment with catestatin time dependently enhances the PACAP-38 effect on mean arterial pressure and enhances sympathetic barosensitivity and chemosensitivity. The time-scale of the effect of catestatin on the response to PACAP-38 strongly suggests that catestatin is either causing changes in gene expression to exert its effects, or modifying intracellular mechanisms normally engaged by PAC1 receptors. The ability of catestatin pretreatment to enhance barosensitivity and chemosensitivity after PACAP-38 injection supports the hypothesis that catestatin manipulates the intracellular environment within sympathetic neurons in a way that increases responses to PACAP.


1995 ◽  
Vol 269 (1) ◽  
pp. E108-E117 ◽  
Author(s):  
B. R. Steenstrup ◽  
P. Alm ◽  
J. Hannibal ◽  
J. C. Jorgensen ◽  
C. Palle ◽  
...  

The distribution, localization, and smooth muscle effects of pituitary adenylate cyclase-activating polypeptide (PACAP) were studied in the human female genital tract. The concentrations of PACAP-38 and PACAP-27 were measured by radioimmunoassays, and both peptides were found throughout the genital tract. The highest concentrations of PACAP-38 were detected in the ovary, the upper part of vagina, and the perineum. The concentrations of PACAP-27 were generally low, in some regions below the detection limit and in other regions 1 to 5% of the PACAP-38 concentrations. Immunocytochemistry revealed that PACAP was located in delicate varicose nerve fibers that were most abundant in the internal cervical os, where they mainly seemed to innervate blood vessels and smooth muscle cells. PACAP-38 and PACAP-27 (10(-10)-10(-6) M) caused a concentration-dependent relaxation of the spontaneous activity of the nonvascular smooth muscle strips from fallopian tube and myometrium in vitro. Likewise, both peptides (10(-10)-10(-6) M) caused relaxation of nonrepinephrine (10(-6) M)-precontracted intramyometrial arteries. No effect of the PACAP sequences, PACAP-(6-27), PACAP-(16-38), and PACAP-(18-27), on fallopian tube was observed. The findings suggest a smooth muscle regulatory role of PACAP in the human female reproductive tract.


2013 ◽  
Vol 57 (3) ◽  
pp. 375-380 ◽  
Author(s):  
Sławomir Gonkowski ◽  
Andrzej Rychlik ◽  
Jarosław Całka

Abstract Changes in the density of mucosal pituitary adenylate cyclase activating peptide-27 -like immunoreactive (PACAP-27 - LI) nerve fibers within various parts of the canine gastrointestinal (GI) tract during inflammatory bowel disease (IBD) were investigated. The distribution of nerves were studied, using a single-labelling immunofluorescence technique, in the mucosal layer of canine stomach, duodenum, jejunum, and descending colon. Canine IBD caused an increase in the density of PACAP- 27-LI mucosal nerves in all studied parts of GI tract. The results suggest that PACAP in the nervous system may be involved in pathological processes during IBD.


2016 ◽  
Vol 233 (17) ◽  
pp. 3269-3277 ◽  
Author(s):  
Attilio Iemolo ◽  
Mariel Seiglie ◽  
Angelo Blasio ◽  
Pietro Cottone ◽  
Valentina Sabino

2016 ◽  
Vol 80 (12) ◽  
pp. 955-964 ◽  
Author(s):  
Rachel J. Donahue ◽  
Archana Venkataraman ◽  
F. Ivy Carroll ◽  
Edward G. Meloni ◽  
William A. Carlezon

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