The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating peptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion

Möller, Kristian; Reimer, Martina Kvist; Ekblad, Eva; Hannibal, Jens; Fahrenkrug, Jan; Kanje, Martin; Sundler, F.

doi:10.1016/s0006-8993(97)00923-2

Cited by 80 publications

(72 citation statements)

References 32 publications

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“…PACAP expression in sensory neurons after nerve injury is known to be changed (35,42,75,76); however, few studies have examined PACAP expression after inflammation (70,77). We have demonstrated an upregulation of PACAP levels in micturition pathways after CYP-induced cystitis (69).…”

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confidence: 65%

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Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes

Braas¹,

May²,

Zvara³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

118

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Pituitary adenylate cyclase activating polypeptide (PACAP) peptides are expressed and regulated in sensory afferents of the micturition pathway. Although these studies have implicated PACAP in bladder control, the physiological significance of these observations has not been firmly established. To clarify these issues, the roles of PACAP and PACAP signaling in micturition and cystitis were examined in receptor characterization and physiological assays. PACAP receptors were identified in various tissues of the micturition pathway, including bladder detrusor smooth muscle and urothelium. Bladder smooth muscle expressed heterogeneously PAC 1null, PAC1HOP1, and VPAC2 receptors; the urothelium was more restricted in expressing preferentially the PAC 1 receptor subtype only. Immunocytochemical studies for PAC 1 receptors were consistent with these tissue distributions. Furthermore, the addition of 50 -100 nM PACAP27 or PACAP38 to isolated bladder strips elicited transient contractions and sustained increases in the amplitude of spontaneous phasic contractions. Treatment of the bladder strips with tetrodotoxin (1 M) did not alter the spontaneous phasic contractions suggesting direct PACAP effects on bladder smooth muscle. PACAP also increased the amplitude of nerve-evoked contractions. By contrast, vasoactive intestinal polypeptide had no direct effects on bladder smooth muscle. In a rat cyclophosphamide (CYP)-induced cystitis paradigm, intrathecal or intravesical administration of PAC 1 receptor antagonist, PACAP6 -38, reduced cystitis-induced bladder overactivity. In summary, these studies support roles for PACAP in micturition and suggest that inflammation-induced plasticity in PACAP expression in peripheral and central micturition pathways contribute to bladder dysfunction with cystitis.neuropeptides; urinary bladder; bladder overactivity; dorsal root ganglia; spinal cord; inflammation THE STORAGE AND PERIODIC ELIMINATION of urine requires a complex neural control system that coordinates the activities of the smooth muscle of the urinary bladder and the smooth and striated muscle of the urethral sphincters (13,32,33). Coordination between these organs is mediated by a complex neural control system located in the brain, spinal cord, and peripheral ganglia (12). Experiments with a chemically (cyclophosphamide, CYP)-induced bladder inflammation (11, 34,38) rodent model have demonstrated alterations in neurochemical (52, 53, 66, 69), electrophysiological (29, 72), organizational (65, 68), and functional properties of the micturition reflex (24, 38, 39), suggesting dramatic reorganization of the micturition reflex pathways. Alterations in peripheral bladder afferent (sensory)/ efferent (autonomic and motor) and central interneuronal pathway functions may underlie detrusor overactivity that accompany CYP-induced cystitis.Pituitary adenylate cyclase activating polypeptide (PACAP) peptides have diverse functions in the endocrine, nervous, gastrointestinal, and cardiovascular systems (1, 6) through PAC 1 , VPAC 1 and VPAC ...

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confidence: 65%

“…High levels of PACAP and vasoactive intestinal polypeptide (VIP) expression have been identified in many CNS neurons and in sensory and autonomic ganglia (1,2,7,42,43,62). Both PACAP and VIP immunoreactivity have been identified in urinary bladder (17,41).…”

mentioning

confidence: 99%

Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes

Braas¹,

May²,

Zvara³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

118

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“…The high potencies of the PACAP peptides at both PAC 1 and VPAC 2 receptors suggest that these peptides may possess regulatory functions on both neuronal and nonneuronal cells in the SCG, while the roles of VIP are predicted to be restricted to nonneuronal cell VPAC 2 receptor activation. Under conditions that result in increased sympathetic neuron PACAP and/or VIP expression, such as neuronal injury (58,59), activation of specific receptor subtypes on SCG neuronal and nonneuronal cells may contribute to the neuronal repair response. PAC 1 receptor activation of both adenylyl cyclase and phospholipase C is characteristic of the group III family of Gprotein-coupled receptors (44,60).…”

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-activating Polypeptides Directly Stimulate Sympathetic Neuron Neuropeptide Y Release through PAC1 Receptor Isoform Activation of Specific Intracellular Signaling Pathways

Braas¹,

May²

1999

Journal of Biological Chemistry

115

127

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Pituitary adenylate cyclase-activating polypeptides (PACAP) have potent regulatory and neurotrophic activities on superior cervical ganglion (SCG) sympathetic neurons with pharmacological profiles consistent for the PACAP-selective PAC 1 receptor. Multiple PAC 1 receptor isoforms are suggested to determine differential peptide potency and receptor coupling to multiple intracellular signaling pathways. The current studies examined rat SCG PAC 1 receptor splice variant expression and coupling to intracellular signaling pathways mediating PACAP-stimulated peptide release. PAC 1 receptor mRNA was localized in over 90% of SCG neurons, which correlated with the cells expressing receptor protein.The neurons expressed the PAC 1 (short)HOP1 receptor but not VIP/PACAP-nonselective VPAC 1 receptors; low VPAC 2 receptor mRNA levels were restricted to ganglionic nonneuronal cells. PACAP27 and PACAP38 potently and efficaciously stimulated both cAMP and inositol phosphate production; inhibition of phospholipase C augmented PACAP-stimulated cAMP production, but inhibition of adenylyl cyclase did not alter stimulated inositol phosphate production. Phospholipase C inhibition blunted neuron peptide release, suggesting that the phosphatidylinositol pathway was a prominent component of the secretory response. These studies demonstrate preferential sympathetic neuron expression of PACAP-selective receptor variants contributing to regulation of autonomic function.The identification of pituitary adenylate cyclase-activating polypeptide (PACAP) 1 and vasoactive intestinal peptide (VIP)/ PACAP receptors has broadened our understanding of the mechanisms underlying the regulatory and neurotrophic roles of this family of peptides. The PACAP precursor molecule is tissue-specifically posttranslationally processed to two biologically active ␣-amidated products, PACAP38 (pro-PACAP-(131-168)) and PACAP27 (pro-PACAP-(131-157)) (1-5), which share amino acid homology with VIP. In the nervous system, PACAP induces neuronal calcium flux, facilitates membrane depolarization, and increases spike frequency (6 -8, 10).2 PACAP peptides also enhance neuroblast survival, proliferation, differentiation, and neurite outgrowth and prevent neuronal apoptosis upon growth factor or stimulus withdrawal and ischemic insult (11-16).The cloning of cDNAs for three putative seven-transmembrane G-protein-coupled receptors for VIP and PACAP demonstrated receptor subtype diversity and functional heterogeneity (17-25). The PACAP-selective PAC 1 receptor demonstrates high affinity for only PACAP38 and PACAP27 and is coupled to multiple intracellular signaling cascades. The VPAC 1 and VPAC 2 receptors, in contrast, exhibit approximate equal high affinity for the PACAP38, PACAP27, and VIP peptides and are coupled to adenylyl cyclase. Multiple PAC 1 receptor isoforms result from the alternative splicing of two exons in the aminoterminal extracellular domain and/or two (HIP and HOP) exons in the third cytoplasmic loop (19,23,24,26). Cell-specific expression of PAC 1 receptor sp...

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“…PACAP is thought to be an important sensory neuropeptide, which was described in the superficial spinal horn layers and in neurons of the dorsal root ganglia (17,22) and can play a role in conduction of sensory stimuli in pain reactions during various pathological processes (15). On the other hand, it is well known that IBD may lead to severe and longlasting pain (3,27).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies also show protective influence of PACAP during pathological processes within the GI tract (4, 7), but the involvement of PACAP occurring within the nervous system of GI tract in such processes is ambiguous. Some studies have reported neuroprotective functions of PACAP in various parts of the nervous system (4,22). However, on the other hand, it does not promote the survival of neurons in myenteric plexus from the small intestine of adult rats (24).…”

Section: Introductionmentioning

confidence: 99%

Pituitary adenylate cyclase activating peptide-27 – like immunoreactive nerve fibers in the mucosal layer of canine gastrointestinal tract in physiology and during inflammatory bowel disease

Gonkowski

Rychlik

Całka

2013

Bulletin of the Veterinary Institute in Pulawy

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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.

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The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating peptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion

Cited by 80 publications

References 32 publications

Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes

Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes

Pituitary Adenylate Cyclase-activating Polypeptides Directly Stimulate Sympathetic Neuron Neuropeptide Y Release through PAC1 Receptor Isoform Activation of Specific Intracellular Signaling Pathways

Pituitary adenylate cyclase activating peptide-27 – like immunoreactive nerve fibers in the mucosal layer of canine gastrointestinal tract in physiology and during inflammatory bowel disease

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