Immunohistochemical localization and distribution of VIP/PACAP receptors in human lung☆

Busto, Rebeca; Prieto, Juan Carlos; Bodega, Guillermo; Zapatero, J.; Carrero, Isabel

doi:10.1016/s0196-9781(99)00202-8

Cited by 50 publications

(43 citation statements)

References 39 publications

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“…[7][8][9][10] Our own preliminary experiments confirmed vasodilatory effects of PACAP on murine pulmonary arteries (L. Hein, unpublished data). Although PAC1 mRNA is expressed in lungs, 5,18 it was not possible to unravel the cellular localization of PAC1 protein in lungs 4 (C. Otto, unpublished data). Obviously, PACAP type II receptors, which are strongly expressed in lung, 4,5 were not able to compensate for the lack of PAC1 and thus, do not seem responsible for mediating the dilatory effects of PACAP on vascular smooth muscle cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…3 Within the lung, PAC1 as well as VPAC1 and VPAC2 mRNA and protein has been detected by immunoblot analysis. 4,5 VPAC1 and VPAC2 proteins are expressed in smooth muscle cells of blood vessels and bronchi. 4 PACAP-positive nerve fibers have been found among smooth muscle bundles in tracheal and bronchial walls and around small blood vessels.…”

mentioning

confidence: 99%

“…4,5 VPAC1 and VPAC2 proteins are expressed in smooth muscle cells of blood vessels and bronchi. 4 PACAP-positive nerve fibers have been found among smooth muscle bundles in tracheal and bronchial walls and around small blood vessels. 6 PACAP as well as VIP exerts dilatory effects on pulmonary blood vessels [7][8][9][10] and bronchi.…”

mentioning

confidence: 99%

“…8,12 Thus, different mechanisms underlying VIP's and PACAP's dilatory effects on pulmonary arteries as well protein expression data support the existence of both PACAP receptor classes within the lung. 4,5 Recently, it has been suggested that VIP could serve as a new drug for treatment of primary pulmonary hypertension. 13 Patients suffering from pulmonary hypertension exhibit reduced VIP levels within their sera and lung tissue, whereas the receptors VPAC1 and VPAC2 are upregulated.…”

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confidence: 99%

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Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

et al. 2004

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Background-Pituitary adenylate cyclase-activating polypeptide (PACAP), acting via 3 different G protein-coupled receptors, has been implicated in the regulation of several homeostatic systems in the body, including cardiopulmonary control. To define the physiologic role of the PACAP-preferring type I receptor, PAC1, in cardiopulmonary function, we developed a mutant mouse strain lacking functional PAC1 receptors. Methods and Results-When PAC1-deficient mice were crossed onto a C57BL/6 background, almost all mutants died during the second postnatal week. Whereas mutant mice were indistinguishable from their wild-type littermates at birth, they showed progressive weakness and died from rapidly developing heart failure. Right ventricles of PAC1 mutants were massively dilated and showed cardiac myocyte hypertrophy, whereas left ventricular structure was unaltered. On direct cardiac catheterization, right ventricular pressure was elevated by 45% in PAC1-deficient mice, indicating increased pulmonary artery pressure, as no malformations were detected in the valves or outflow tract of the right ventricle. Consistent with elevated pulmonary pressure, lung capillary density was decreased by 30% and small pulmonary arteries of mutant mice had significant vascular smooth muscle cell hypertrophy compared with wild-type mice. Conclusions-Whereas PACAP induces vasodilation in isolated pulmonary vessels in wild-type mice, the absence of its specific receptor PAC1 causes pulmonary hypertension and right heart failure after birth. These in vivo findings demonstrate the crucial importance of PAC1-mediated signaling for the maintenance of normal pulmonary vascular tone during early postnatal life.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

et al. 2004

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“…The two subtypes of receptors for VIP, VPAC1 and VPAC2, are abundant in many types of human cancers (5)(6)(7)11,12,20,27). In the human lung, the presence of VPAC receptors has been demonstrated by RT-PCR, immunoblotting and immunohistochemical staining (28,29). There is also growing evidence of the importance of neuropeptides in the pathophysiology and progression of human lung cancer.…”

Section: Cancer Tissuementioning

confidence: 99%

Gene expression of vasoactive intestinal peptide receptors in human lung cancer

et al. 2011

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Abstract. Despite significant improvement in the diagnosis and treatment of various human carcinomas, the 5-year survival rate for lung cancer remains below 20%. Vasoactive intestinal peptide (VIP) is an important neuropeptide in the control of lung physiology, and exerts its functions mainly through two receptor subtypes, VPAC1 and VPAC2. Receptors for VPAC1 and VPAC2 are present in human lung cancer cells, but very limited information exists about the mRNA expression of these VIP receptor subtypes in lung cancer specimens. The aim of the present study was to investigate by RT-PCR the mRNA expression of the VPAC1 and VPAC2 receptors in surgical specimens of 43 human lung cancer specimens and 7 normal lung samples. mRNA expression of the VPAC1 receptor was detected in 51% of the tumor specimens, while the incidence of mRNA expression for VPAC2 was 46%. Twenty-one percent of the tumor samples expressed only the VPAC1 receptor and 16% displayed only the VPAC2 receptor, while 13 samples (30%) expressed neither subtype. Thirteen cancer tissue specimens (30%), expressed both of these VIP receptor subtypes. Three normal lung tissue specimens also displayed gene expression for VPAC1 and/or VPAC2 receptors. Our results support the additional investigation of the role of VIP and its receptors in human lung cancer and suggest a further development of VIP analogs for therapeutic and imaging purposes in this malignancy.

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VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS-CoV-2-infected cells

Temerozo

Sacramento

Fintelman-Rodrigues

et al. 2022

Journal of Leukocyte Biology

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Infection by SARS‐CoV‐2 may elicit uncontrolled and damaging inflammatory responses. Thus, it is critical to identify compounds able to inhibit virus replication and thwart the inflammatory reaction. Here, we show that the plasma levels of the immunoregulatory neuropeptide VIP are elevated in patients with severe COVID‐19, correlating with reduced inflammatory mediators and with survival on those patients. In vitro, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP), highly similar neuropeptides, decreased the SARS‐CoV‐2 RNA content in human monocytes and viral production in lung epithelial cells, also reducing cell death. Both neuropeptides inhibited the production of proinflammatory mediators in lung epithelial cells and in monocytes. VIP and PACAP prevented in monocytes the SARS‐CoV‐2‐induced activation of NF‐kB and SREBP1 and SREBP2, transcriptions factors involved in proinflammatory reactions and lipid metabolism, respectively. They also promoted CREB activation, a transcription factor with antiapoptotic activity and negative regulator of NF‐kB. Specific inhibition of NF‐kB and SREBP1/2 reproduced the anti‐inflammatory, antiviral, and cell death protection effects of VIP and PACAP. Our results support further clinical investigations of these neuropeptides against COVID‐19.

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Immunohistochemical localization and distribution of VIP/PACAP receptors in human lung☆

Cited by 50 publications

References 39 publications

Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase–Activating Polypeptide Type I Receptor–Deficient Mice

Gene expression of vasoactive intestinal peptide receptors in human lung cancer

VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS-CoV-2-infected cells

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