Evidence for the involvement of VPAC1 and VPAC2 receptors in pressure‐induced vasodilatation in rodents

Fizanne, Lionel; Sigaudo‐Roussel, Dominique; Saumet, J. L.; Fromy, Bérengère

doi:10.1113/jphysiol.2003.053835

Cited by 44 publications

(32 citation statements)

References 45 publications

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“…The PAC1 receptor is important in renin secretion (21) and PACAP-induced depolarizations in superior cervical ganglion neurons (1). The VPAC1 receptor, on the other hand, is necessary for pressureinduced vasodilatation (11), and evidence from our present study suggests that it may be primarily involved in the MAP response observed after intrathecal infusion of PACAP-38.…”

Section: Discussionmentioning

confidence: 49%

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Farnham

Inglott

Pilowsky

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Farnham MM, Inglott MA, Pilowsky PM. Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 300: H214 -H222, 2011. First published October 15, 2010 doi:10.1152/ajpheart.00662.2010.-The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclaseactivating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6 -38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6 -38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined. sympathetic activity; spinal cord; pituitary adenylate cyclase-activating polypeptide THE ROSTRAL VENTROLATERAL MEDULLA (RVLM) is crucial for the tonic and reflex control of the cardiovascular system (see Refs. 15 and 43 for reviews). RVLM presympathetic neurons are commonly defined as being inhibited following baroreceptor activation and having a spinal axon (2, 28, 29). Neurochemically, 60 -80% of presympathetic neurons are C1 neurons (29,42,48,49), having all of the enzymes required for adrenaline synthesis. Presympathetic RVLM neurons project monosynaptically to sympathetic preganglionic neurons (SPN) in the intermediolateral (IML) cell column of the spinal cord (34,38). SPN, in turn, regulate the activity of the heart, kidneys, blood vessels, and adrenal chromaffin cells, thereby determining sympathetic outflow and ultimately blood pressure.Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory 38-amino-acid peptide originally identified in ovine hypothalamus (32) that also exists as a...

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Section: Discussionmentioning

confidence: 49%

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Farnham

Inglott

Pilowsky

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…18 VIP induces its receptor-mediated inhibitory effect on the smooth muscle cell by activating adenylate cyclase and stimulating cAMP production through VPAC1 and VPAC2 receptors, both of which are blocked by the competitive VIP antagonist we used. 26,27 However, VIP also induces production and release of NO from the presynaptic neuron; in addition, VIP has been reported to induce NO production in the smooth muscle cell by activation of the natriuretic peptide clearance receptor. 28 In contrast to our previous work in longitudinal muscle in younger rats, 16 antagonist nor by L-NNA in the current study.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Extrinsic Denervation on VIP and Substance P Innervation in Circular Muscle of Rat Jejunum

Kasparek

Fatima

Iqbal

et al. 2007

Journal of Gastrointestinal Surgery

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Intestinal denervation contributes to enteric motor dysfunction after small bowel transplantation (SBT). Our aim was to determine long-term effects of extrinsic denervation on function of nonadrenergic, noncholinergic innervation with substance P and vasoactive intestinal polypeptide (VIP). Contractile activity of jejunal circular muscle strips from six age-matched, naive control rats (NC) and eight rats 1 year after syngeneic SBT was studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently to a comparable degree in both groups. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) and the nitric oxide synthase inhibitor L-NG-nitro-arginine did not affect VIP-induced inhibition but increased contractile activity during electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than SBT. The substance P antagonist ([D-Pro(2),D-Trp(7,9)]-substance P) inhibited effects of exogenous substance P and decreased the excitatory EFS response. Immunohistofluorescence showed tyrosine hydroxylase staining after SBT indicating sympathetic reinnervation. In jejunal circular muscle after chronic denervation, response to exogenous substance P, but not VIP, is decreased, whereas endogenous release of both neurotransmitters is preserved. Alterations in balance of excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.

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“…1B, VIP increased LNCaP cell proliferation in a dose-dependent manner (EC 50 ϭ 6.7 Ϯ 2.4 nM) with a maximum of approximately 75% of that in the presence of an optimal concentration of DHT (20 nM). A 2 M concentration of the VPAC-R antagonist [D-P-Cl-Phe(6)-Leu(17)]-VIP (Fizanne et al, 2004) blocked VIP-induced LNCaP cell proliferation, but not DHTstimulation (Fig. 1C), suggesting that VIP stimulates prostate cancer growth through VPAC-Rs in an androgen-independent manner, as seen in hormone-refractory prostate cancers.…”

Section: Downloaded Frommentioning

confidence: 97%

Vasoactive Intestinal Peptide Transactivates the Androgen Receptor through a Protein Kinase A-Dependent Extracellular Signal-Regulated Kinase Pathway in Prostate Cancer LNCaP Cells

Xie

Wolff

Lin³

et al. 2007

Mol Pharmacol

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Acquisition of androgen independence by prostate cancer is the key problem of prostate cancer progression. Vasoactive intestinal peptide (VIP), a neuropeptide, may act as a survival factor for prostate cancer cells under androgen deprivation. However, the molecular mechanisms by which VIP promotes the androgenindependent growth of androgen-sensitive prostate cancer cells have not been addressed. We therefore investigated the biological effect and signal pathway of VIP in LNCaP cells, a prostate cancer cell line that requires androgens for growth. We showed that low nanomolar concentrations of VIP, acting through G s -protein-coupled VIP receptors, can induce LNCaP cell growth in the absence of androgen. Blockade of androgen-receptor (AR) in these cells by AR antagonist bicalutamide or by anti-AR small interfering RNA, inhibited the proliferative effect of VIP. In addition, VIP stimulated androgen-independent activation of AR with an EC 50 of 3.0 Ϯ 0.8 nM. We then investigated VIP-stimulated signaling events that may interact with the AR pathway in prostate cancer cells. VIP regulation of AR activation, mediated by VIP receptors, was protein kinase A (PKA)-dependent, and extracellular signal-regulated kinase 1/2 (ERK1/2) activation contributes to VIP-mediated AR activation. Furthermore, PKA-dependent Rap1 activation is required for both ERK1/2 activation and androgen-independent AR activation in LNCaP cells upon VIP stimulation. Finally, we showed that VIP-induced AR activation was also present in prostate cancer CWR22Rv1 and PC3 cells transfected with the wild-type AR. Altogether, we demonstrate that VIP acting through its G s -proteincoupled receptors can cause androgen-independent transactivation of AR through a PKA/Rap1/ERK1/2 pathway, thus promoting androgen-independent proliferation of androgen-sensitive prostate cancer cells.Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men and the second leading cause (after lung) of cancer mortality. In its early stages, prostate cancer cell growth is dependent on androgens and their androgen receptor (AR), a member of the nuclear receptor superfamily (Heinlein and Chang, 2004). Thus, androgen-deprivation therapies that block AR activation cause repression of prostate tumors. Unfortunately, the majority of prostate cancers eventually transit from being androgen-dependent to androgen-independent (hormone refractory), making androgen-deprivation therapies ineffective (Feldman and Feldman, 2001).The precise mechanisms underlying this conversion of

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Evidence for the involvement of VPAC1 and VPAC2 receptors in pressure‐induced vasodilatation in rodents

Cited by 44 publications

References 45 publications

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Long-Term Effects of Extrinsic Denervation on VIP and Substance P Innervation in Circular Muscle of Rat Jejunum

Vasoactive Intestinal Peptide Transactivates the Androgen Receptor through a Protein Kinase A-Dependent Extracellular Signal-Regulated Kinase Pathway in Prostate Cancer LNCaP Cells

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