Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries

Prieto, Dolores; Arcos, Luis Rivera de los; Martínez, Pilar; Benedito, Sara; García‐Sacristán, Albino; Hernández, Medardo

doi:10.1038/sj.bjp.0706005

Cited by 14 publications

(11 citation statements)

References 39 publications

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“…27 We have recently provided an explanation for this controversy between the rich presence of NPY-containing nerves in the penis and the lack of clear antierectile/vasoconstrictor effects of the peptide. 26 Thus, NPY was found to have a dual facilitatory/inhibitory role on the noradrenergic vasoconstriction of horse penile resistance arteries, the ability to enhance and decrease noradrenaline-induced contractions being achieved through a heterogenous population of NPY receptors. Both Y 1 -and Y 2 -postsynaptic receptors are involved in the NPY-induced enhancement of noradrenaline contractions, and presynaptic inhibitory Y 2 receptors limit noradrenaline release from (Figure 1).…”

Section: Physiological Regulation Of Penile Vasoconstrictionmentioning

confidence: 99%

“…20 Neuropeptide Y (NPY), a 36-amino acid peptide usually colocalized with noradrenaline in sympathetic perivascular nerves, is widely distributed in penile erectile tissues with a particularly high density around helicine arteries. 12,25,26 Although NPY was initially suggested to have a role in detumescence, 20 earlier in vitro studies showed either no effect of NPY in strips of human CC and cavernous artery or inconsistent contractions in penile circumflex veins. 4,12 Moreover, intracavernous injection of NPY increased intracavernous pressure and caused penile tumescence in rabbits.…”

Section: Physiological Regulation Of Penile Vasoconstrictionmentioning

confidence: 99%

“…28,29 Under conditions of Y 1 and Y 2 receptor blockade, NPY can also induce NO-independent relaxations in penile resistance arteries through atypical receptors located at the endothelium, which could account for the in vivo proerectogenic effects reported for the peptide. 26 …”

Section: Physiological Regulation Of Penile Vasoconstrictionmentioning

confidence: 99%

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Physiological regulation of penile arteries and veins

2007

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Recent experimental evidence suggests that arterial insufficiency precedes the structural and functional changes in corpora cavernosa (CC) leading to organic erectile dysfunction (ED). The present review gives an overview of the physiological factors involved in the regulation of penile vasculature. Sympathetic nerves maintain flaccidity and tonically released noradrenaline induces vasoconstriction of both arteries and veins through a 1 -and a 2 -postsynaptic receptors and downregulates its own release and that of nitric oxide (NO) through a 2 -presynaptic receptors. The sympathetic cotransmitter neuropeptide Y (NPY) modulates noradrenergic vasoconstriction in penile small arteries by both enhancing and depressing noradrenaline contractions through Y 1 -and Y 2 -postsynaptic and a NO-independent atypical endothelial receptor, respectively. Activation of a 1 -adrenoceptors involves both Ca 2 þ influx through L-type and receptor-operated Ca 2 þ channels (ROC) and Ca 2 þ sensitization mechanisms mediated by protein kinase C (PKC), tyrosine kinases (TKs) and Rho kinase (RhoK). In addition, RhoK can regulate Ca 2 þ entry in penile arteries upon receptor stimulation. Vasodilatation of penile arteries and large veins during erection is mediated by neurally released NO. The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS). NO stimulates guanylate cyclase and increased cyclic guanin 3 0 -monophosphate (cGMP) levels in turn activate protein kinase G (PKG), which enhances K þ efflux through Ca 2 þ -activated (K Ca ) and voltage-dependent Ca 2 þ (K v ) channels in penile arteries and veins, respectively. PKG-mediated decrease in Ca 2 þ sensitivity and its regulation by RhoK remains to be clarified in penile vasculature. Phosphodiesterase type 5 (PDE5) inhibitors are potent vasodilators of penile resistance arteries and increase the content and effects of basally released endothelial NO. Endothelium-dependent relaxations of penile small arteries also include an endothelium-derived hyperpolarizing factor (EDHF)-type response, which is impaired in diabetes and hypertension-associated ED. Locally produced contractile and relaxant prostanoids regulate penile venous and arterial tone, respectively. The latter activates prostaglandin I (IP) and prostaglandin E (EP) receptors coupled to adenylate cyclase and to the increase of cyclic adenosine monophosphate (cAMP) levels, which in turn stimulates K þ efflux through ATPsensitive K þ (K ATP ) channels. There is a crosstalk between the cGMP and cAMP signaling pathways in penile small arteries. Relevant issues such as the mechanisms underlying the excitationsecretion coupling of the endothelial cells, as well as those involved in cell proliferation and vascular remodeling of the penile vasculature remain to be elucidated. In addition, only few studies have investigated the changes in structure and function of penile a...

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Section: Physiological Regulation Of Penile Vasoconstrictionmentioning

confidence: 99%

Section: Physiological Regulation Of Penile Vasoconstrictionmentioning

confidence: 99%

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Physiological regulation of penile arteries and veins

2007

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“…The anti-NPY antibody employed in this study was previously found to show specificity by preadsorption test in the horse urogenital system (Prieto et al, 1997(Prieto et al, , 2004. The immunogen utilized was synthetic porcine NPY (Table 1).…”

Section: Antibody Characterization Specificity Of Primary Antibodiesmentioning

confidence: 99%

Sympathetic innervation of the ileocecal junction in horses

Russo

Bombardi

Grandis

et al. 2010

J of Comparative Neurology

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The distribution and chemical phenotypes of sympathetic and dorsal root ganglion (DRG) neurons innervating the equine ileocecal junction (ICJ) were studied by combining retrograde tracing and immunohistochemistry. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) was investigated. Sympathetic neurons projecting to the ICJ were distributed within the celiac (CG), cranial mesenteric (CranMG), and caudal mesenteric (CaudMG) ganglia, as well as in the last ganglia of the thoracic sympathetic chain and in the splanchnic ganglia. In the CG and CranMG 91 +/- 8% and 93 +/- 12% of the neurons innervating the ICJ expressed TH- and DBH-IR, respectively. In the CaudMG 90 +/- 15% and 94 +/- 5% of ICJ innervating neurons were TH- and DBH-IR, respectively. Sympathetic (TH-IR) fibers innervated the myenteric and submucosal ganglia, ileal blood vessels, and the muscle layers. They were more concentrated at the ICJ level and were also seen encircling myenteric plexus (MP) and submucosal plexus (SMP) descending neurons that were retrogradely labeled from the ICJ. Among the few retrogradely labeled DRG neurons, nNOS-, CGRP-, and SP-IR nerve cells were observed. Dense networks of CGRP-, nNOS-, and SP-IR varicosities were seen around retrogradely labeled prevertebral ganglia neurons. The CGRP-IR fibers are probably the endings of neurons projecting from the intestine to the prevertebral ganglia. These findings indicate that this crucial region of the intestinal tract is strongly influenced by the sympathetic system and that sensory information of visceral origin influences the sympathetic control of the ICJ.

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“…penile arteries; calcium entry; nonselective cation channels; calcium sensitization PENILE ERECTION OCCURS when nitric oxide (NO) released from nerves and endothelium upon sexual stimulation relaxes smooth muscle of the corpus cavernosum (CC) and penile arteries, leading to blood filling of the sinuses and restriction of venous outflow (2, 25). During the flaccid state, erectile tissue is contracted by the release of neural and local factors, such as norepinephrine, neuropeptide Y, endothelin-1, and prostanoids that increase smooth muscle cytosolic Ca 2ϩ ([Ca 2ϩ ] i ) and/or Ca 2ϩ sensitization through activation G protein-coupled receptors (2,20,25). Erectile dysfunction (ED), considered as a sign of early endothelial dysfunction and cardiovascular disease, is three times more prevalent in men with Types 1 and 2 diabetes than in men without diabetes (3, 33).…”

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confidence: 99%

Rho kinase is involved in Ca²⁺ entry of rat penile small arteries

Villalba¹,

Stankevičius²,

Simonsen³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Tonic physiological activity of RhoA/Rho kinase contributes to the maintenance of penile flaccidity through its involvement in the Ca 2ϩ sensitization of erectile tissue smooth muscle. The present study hypothesized that Rho kinase is also involved in the modulation of Ca 2ϩ entry induced by ␣1-adrenoceptor stimulation of penile arteries. Rat penile arteries were mounted in microvascular myographs for simultaneous measurements of intracellular Ca 2ϩ ([Ca 2ϩ ]i) and force. The Rho-kinase inhibitor Y-27632 markedly reduced norepinephrine-mediated electrically induced contractions and the increases in both [Ca 2ϩ ]i and tension elicited by the ␣1-adrenoceptor agonist phenylephrine (Phe). In contrast, the protein kinase C (PKC) inhibitor Ro-31-8220 reduced tension without altering the Phe-induced increase in [Ca 2ϩ ]i. In the presence of nifedipine, Y-27632 still inhibited the non-L-type Ca 2ϩ signal and blunted Phe contraction. Y-27632 did not impair the capacitative Ca 2ϩ entry evoked by store depletion with cyclopiazonic acid but largely reduced the Ba 2ϩ influx stimulated by Phe in fura-2 AM-loaded arteries. The addition of Y-27632 to arteries depolarized with high KCl markedly reduced tension without changing [Ca 2ϩ ]i. In ␣-toxin-permeabilized penile arteries stimulated with threshold Ca 2ϩ concentrations, Y-27632 inhibited the sensitization induced by either guanosine 5Ј-O-(3-thiotriphosphate) (GTP␥S) or Phe in the presence of GTP␥S. However, Y-27632 failed to alter contractions induced by a maximal concentration of free Ca 2ϩ . These results suggest that Rho kinase, besides its contribution to the Ca 2ϩ sensitization of the contractile proteins, is also involved in the regulation of Ca 2ϩ entry through a nonselective cation channel activated by ␣1-adenoceptor stimulation in rat penile arteries. penile arteries; calcium entry; nonselective cation channels; calcium sensitization PENILE ERECTION OCCURS when nitric oxide (NO) released from nerves and endothelium upon sexual stimulation relaxes smooth muscle of the corpus cavernosum (CC) and penile arteries, leading to blood filling of the sinuses and restriction of venous outflow (2, 25). During the flaccid state, erectile tissue is contracted by the release of neural and local factors, such as norepinephrine, neuropeptide Y, endothelin-1, and prostanoids that increase smooth muscle cytosolic Ca 2ϩ ([Ca 2ϩ ] i ) and/or Ca 2ϩ sensitization through activation G protein-coupled receptors (2,20,25). Erectile dysfunction (ED), considered as a sign of early endothelial dysfunction and cardiovascular disease, is three times more prevalent in men with Types 1 and 2 diabetes than in men without diabetes (3, 33). About 50% of these patients exhibit suboptimal responses to oral phophodiestarase 5 inhibitors, such as sildenafil (33), that enhance the NOmediated vasodilatation leading to penile erection. As an alternative, inhibition of the Rho/Rho-kinase signaling pathway has been proposed as a potential molecular target for the development of novel therapies for ED si...

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Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries

Cited by 14 publications

References 39 publications

Physiological regulation of penile arteries and veins

Physiological regulation of penile arteries and veins

Sympathetic innervation of the ileocecal junction in horses

Rho kinase is involved in Ca²⁺ entry of rat penile small arteries

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Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries

Cited by 14 publications

References 39 publications

Physiological regulation of penile arteries and veins

Physiological regulation of penile arteries and veins

Sympathetic innervation of the ileocecal junction in horses

Rho kinase is involved in Ca2+ entry of rat penile small arteries

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Rho kinase is involved in Ca²⁺ entry of rat penile small arteries