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Jan Fahrenkrug - One of the best experts on this subject based on the ideXlab platform.
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Expression and characterization of preproVIP derived Peptides in the human male urogenital tract.
Neuropeptides, 1995Co-Authors: B. Ottesen, H.e Bredkjaer, E Ekblad, S Krause, J Miskowiak, Jan FahrenkrugAbstract:Abstract Expression of the gene sequence encoding vasoactive intestinal polyPeptide (VIP) leads to the synthesis of a 170 amino acid precursor molecule which can be processed to five fragments: preproVIP 22–79, Peptide Histidine methionine (PHM), or Peptide Histidine Valine (PHV), preproVIP 111–122, VIP and preproVIP 156–170. Using region specific radioimmunoassays and antisera against the functional domains of the VIP precursor in combination with immunocytochemistry and chromatography, the localization, distribution and identify of the preproVIP derived Peptides within the human male urogenital tract were investigated. Postmortem as well as fresh tissue specimens were used. All the preproVIP derived Peptides were expressed and could be demonstrated in nerve fibres throughout the urogenital tract in close relation to the epithelial lining and in vascular as well as non-vascular smooth muscle. The VIP-related Peptide containing fibres were most abundant in the prostate parenchyma and the seminal vesicle. Using double immunostaining, co-localization of the various preproVIP derived Peptides could be evidenced. The fact that all preproVIP derived Peptides are present in the urogenital tract, should be taken into consideration when the regulatory aspects of neuroPeptides in physiological and pathophysiological functions are discussed.
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All prepro-VIP-derived Peptides, except , are expressed in the female rat anterior pituitary and increased by estrogen
Peptides, 1995Co-Authors: Marie Louise Skakkebæk, Jens D. Mikkelsen, Bent Ottesen, Birgitte Georg, Jan FahrenkrugAbstract:The expression of VIP precursor products: prepro-VIP(22-79), Peptide Histidine isoleucine (PHI), Peptide Histidine Valine (PHV), prepro-VIP(111-122), VIP, prepro-VIP(156-170), and prepro-VIP mRNA in the anterior pituitary of estrogen-treated, ovariectomized rats, of ovariectomized controls, and of sham-operated controls was examined. Using radioimmunoassays based on antisera against each of the prepro-VIP sequences, we found that all sequences were expressed and markedly induced by estrogen, except PHI and PHV, which both were undetectable. By immunohistochemistry, it appeared that the number of cells immunoreactive for each of these sequences was increased in the estrogen-treated animals. However, PHI/PHV-immunoreactive cells could not be detected, despite the use of four different PHI antisera with different specificities. Estrogen treatment increased the prepro-VIP mRNA as judged by Northern blotting. In situ hybridization signals for both VIP mRNA and PHI mRNA were observed in few pituitary cells from control animals whereas strong positive signals were observed in a larger number of cells after estrogen treatment. The findings show that estrogen causes activation of the VIP gene expression in anterior pituitary cells, and that the absence of PHI and PHV probably is due to translational or posttranslational events.
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Concentrations and distribution of vasoactive intestinal Peptide (VIP), Peptide Histidine isoleucine (PHI) and Peptide Histidine Valine (PHV) in the cerebral cortex and the suprachiasmatic nucleus of the mouse
Brain research, 1994Co-Authors: Jens D. Mikkelsen, Jan FahrenkrugAbstract:Abstract Prepro-vasoactive intestinal Peptide (prepro-VIP) is processed to at least three biologically active Peptides: VIP, Peptide Histidine isoleucine (PHI) and an extended PHI, Peptide Histidine Valine (PHV). The aim of the present investigation was by chromatography combined with RIA and immunocytochemistry to determine which of these Peptides were present in the cerebral cortex and the hypothalamic suprachiasmatic nucleus (SCN) of the mouse. These regions were chosen since they are known to contain a high concentration of VIP but the relative concentration of PHI and PHV is not known. Tissue was extracted and subjected to gel chromatography and high-pressure liquid chromatography (HPLC). VIP and PHI immunoreactivities co-eluted with synthetic rat VIP and PHI. A minor peak of PHI and prepro-VIP(111–122) immunoreactivities eluted at the position of synthetic PHV. Surprisingly, a major peak of prepro-VIP(111–122) immunoreactivity eluted in a position not related to any other immunoreactivity indicating the presence of prepro-VIP(111–122). Measurements of these immunoreactivities in cortical and suprachiasmatic extracts revealed that VIP was found in the highest concentration whereas PHV was found in the lowest. Immunoreactivity for PHI and prepro-VIP(111–122) was found in moderate concentrations. Except for prepro-VIP(111–122) which was found to be ∼3×higher concentrated in the SCN than in the cerebral cortex, the other immunoreactivities were found in almost similar relative concentrations in the two tissues. Using immunocytochemistry, elongated neurons mostly of the bipolar type with prominent processes observed in the cerebral cortex reacted with all antisera tested. More PHI/PHV/prepro-VIP(111–122)- than VIP-immunoreactive (ir) nerve fibers were found in the cerebral cortex. In the SCN, the density of immunoreactivity was the same whatever antiserum used. VIP-, PHI- and prepro-VIP(111–122)/PHV-ir neurons were observed in the ventral part of the nucleus with numerous axons coursing caudodorsally into the subparaventricular area. A substantial number of terminals was detected caudal to the paraventricular nucleus. Minor projections spread to the medial part of the anterior nucleus and to the medial preoptic area hypothalamic. These data show that VIP and PHI are the major active Peptides derived from prepro-VIP in the mouse cerebral cortex and SCN whereas PHV was found in minor concentrations. Prepro-VIP(111–122), which so far has been found to have no functional significance, is, therefore, most likely a vaste fragment of processing of PHI in central neurons. The presence of all these Peptides in axons indicate that the neurotransmission involving VIP is more complex, due to roles of other Peptides processed from the same prepro-VIP molecule.
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Peptide Histidine Valine (PHV) is present and biologically active in the human female genital tract.
Regulatory peptides, 1992Co-Authors: C. Palle, Bent Ottesen, Jan FahrenkrugAbstract:The occurrence of vasoactive intestinal polyPeptide (VIP), Peptide Histidine methionine (PHM) and Peptide Histidine Valine (PHV) in the human female genital tract was studied by means of radioimmunoassay in combination with gel chromatography. In addition, the effect of PHV on genital smooth muscle activity was investigated in vitro and compared to that of VIP. Immunoreactive VIP, PHM and PHV were present in all regions of the human female genital tract, the highest concentrations being measured in the vagina and the uterine cervix. The Peptides displayed similar regional distribution and as expected from the structure of the VIP precursor molecule in which the examined Peptides are contained, the molar ratio of VIP to the total PHM/PHV immunoreactivity was close to 1:1. In all regions PHV constituted 50-70% of the total PHM/PHV immunoreactivity indicating that the dibasic conversion site after PHM was uncleaved. VIP and PHV were found to be equipotent relaxants of the smooth muscle from the Fallopian tube and the myometrium. The present study indicates that PHV like PHM and VIP may act as a neurotransmitter in the human female genital tract and thus participate in the local nervous control of the reproductive functions.
Jens D. Mikkelsen - One of the best experts on this subject based on the ideXlab platform.
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All prepro-VIP-derived Peptides, except , are expressed in the female rat anterior pituitary and increased by estrogen
Peptides, 1995Co-Authors: Marie Louise Skakkebæk, Jens D. Mikkelsen, Bent Ottesen, Birgitte Georg, Jan FahrenkrugAbstract:The expression of VIP precursor products: prepro-VIP(22-79), Peptide Histidine isoleucine (PHI), Peptide Histidine Valine (PHV), prepro-VIP(111-122), VIP, prepro-VIP(156-170), and prepro-VIP mRNA in the anterior pituitary of estrogen-treated, ovariectomized rats, of ovariectomized controls, and of sham-operated controls was examined. Using radioimmunoassays based on antisera against each of the prepro-VIP sequences, we found that all sequences were expressed and markedly induced by estrogen, except PHI and PHV, which both were undetectable. By immunohistochemistry, it appeared that the number of cells immunoreactive for each of these sequences was increased in the estrogen-treated animals. However, PHI/PHV-immunoreactive cells could not be detected, despite the use of four different PHI antisera with different specificities. Estrogen treatment increased the prepro-VIP mRNA as judged by Northern blotting. In situ hybridization signals for both VIP mRNA and PHI mRNA were observed in few pituitary cells from control animals whereas strong positive signals were observed in a larger number of cells after estrogen treatment. The findings show that estrogen causes activation of the VIP gene expression in anterior pituitary cells, and that the absence of PHI and PHV probably is due to translational or posttranslational events.
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Concentrations and distribution of vasoactive intestinal Peptide (VIP), Peptide Histidine isoleucine (PHI) and Peptide Histidine Valine (PHV) in the cerebral cortex and the suprachiasmatic nucleus of the mouse
Brain research, 1994Co-Authors: Jens D. Mikkelsen, Jan FahrenkrugAbstract:Abstract Prepro-vasoactive intestinal Peptide (prepro-VIP) is processed to at least three biologically active Peptides: VIP, Peptide Histidine isoleucine (PHI) and an extended PHI, Peptide Histidine Valine (PHV). The aim of the present investigation was by chromatography combined with RIA and immunocytochemistry to determine which of these Peptides were present in the cerebral cortex and the hypothalamic suprachiasmatic nucleus (SCN) of the mouse. These regions were chosen since they are known to contain a high concentration of VIP but the relative concentration of PHI and PHV is not known. Tissue was extracted and subjected to gel chromatography and high-pressure liquid chromatography (HPLC). VIP and PHI immunoreactivities co-eluted with synthetic rat VIP and PHI. A minor peak of PHI and prepro-VIP(111–122) immunoreactivities eluted at the position of synthetic PHV. Surprisingly, a major peak of prepro-VIP(111–122) immunoreactivity eluted in a position not related to any other immunoreactivity indicating the presence of prepro-VIP(111–122). Measurements of these immunoreactivities in cortical and suprachiasmatic extracts revealed that VIP was found in the highest concentration whereas PHV was found in the lowest. Immunoreactivity for PHI and prepro-VIP(111–122) was found in moderate concentrations. Except for prepro-VIP(111–122) which was found to be ∼3×higher concentrated in the SCN than in the cerebral cortex, the other immunoreactivities were found in almost similar relative concentrations in the two tissues. Using immunocytochemistry, elongated neurons mostly of the bipolar type with prominent processes observed in the cerebral cortex reacted with all antisera tested. More PHI/PHV/prepro-VIP(111–122)- than VIP-immunoreactive (ir) nerve fibers were found in the cerebral cortex. In the SCN, the density of immunoreactivity was the same whatever antiserum used. VIP-, PHI- and prepro-VIP(111–122)/PHV-ir neurons were observed in the ventral part of the nucleus with numerous axons coursing caudodorsally into the subparaventricular area. A substantial number of terminals was detected caudal to the paraventricular nucleus. Minor projections spread to the medial part of the anterior nucleus and to the medial preoptic area hypothalamic. These data show that VIP and PHI are the major active Peptides derived from prepro-VIP in the mouse cerebral cortex and SCN whereas PHV was found in minor concentrations. Prepro-VIP(111–122), which so far has been found to have no functional significance, is, therefore, most likely a vaste fragment of processing of PHI in central neurons. The presence of all these Peptides in axons indicate that the neurotransmission involving VIP is more complex, due to roles of other Peptides processed from the same prepro-VIP molecule.
C. Tanaka - One of the best experts on this subject based on the ideXlab platform.
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Low cerebrospinal fluid concentrations of Peptide Histidine Valine and somatostatin-28 in Alzheimer's disease: Altered processing of prepro-vasoactive intestinal Peptide and prepro-somatostatin
Neuropeptides, 1995Co-Authors: Minoru Yasuda, Naoto Minamitani, Kiyoshi Maeda, T Kakigi, T Kawaguchi, C. TanakaAbstract:Recent studies have indicated that deposition of beta amyloid Peptide in the brains of patients with senile dementia of the Alzheimer type (SDAT) is a consequence of abnormal processing of the beta amyloid protein precursor. In addition, reduced concentrations of various Peptides have been measured in post-mortem brain tissue and cerebrospinal fluid (CSF) of patients with SDAT. We determined concentrations of the Peptides derived from prepro-vasoactive intestinal Peptide (VIP)--Peptide Histidine methionine-27 (PHM-27), Peptide Histidine Valine (PHV) and VIP--and Peptides derived from prepro-somatostatin (prepro-SS), SS-14 and SS-28, in CSF of patients with SDAT by radioimmunoassay combined with high performance liquid chromatography. We found significantly reduced levels of total PHM-immunoreactivity (IR) and PHV, and unaltered levels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, while SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-Peptides of VIP and SS may occur in SDAT and that these alterations might have a significant role in the pathogenesis of SDAT.
Minoru Yasuda - One of the best experts on this subject based on the ideXlab platform.
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Low cerebrospinal fluid concentrations of Peptide Histidine Valine and somatostatin-28 in Alzheimer's disease: Altered processing of prepro-vasoactive intestinal Peptide and prepro-somatostatin
Neuropeptides, 1995Co-Authors: Minoru Yasuda, Naoto Minamitani, Kiyoshi Maeda, T Kakigi, T Kawaguchi, C. TanakaAbstract:Recent studies have indicated that deposition of beta amyloid Peptide in the brains of patients with senile dementia of the Alzheimer type (SDAT) is a consequence of abnormal processing of the beta amyloid protein precursor. In addition, reduced concentrations of various Peptides have been measured in post-mortem brain tissue and cerebrospinal fluid (CSF) of patients with SDAT. We determined concentrations of the Peptides derived from prepro-vasoactive intestinal Peptide (VIP)--Peptide Histidine methionine-27 (PHM-27), Peptide Histidine Valine (PHV) and VIP--and Peptides derived from prepro-somatostatin (prepro-SS), SS-14 and SS-28, in CSF of patients with SDAT by radioimmunoassay combined with high performance liquid chromatography. We found significantly reduced levels of total PHM-immunoreactivity (IR) and PHV, and unaltered levels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, while SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-Peptides of VIP and SS may occur in SDAT and that these alterations might have a significant role in the pathogenesis of SDAT.
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Peptide Histidine methionine and vasoactive intestinal Peptide levels in human cerebrospinal fluid: age-related changes and absence of a correlation with serum prolactin.
Regulatory peptides, 1993Co-Authors: Minoru Yasuda, Naoto Minamitani, Kiyoshi Maeda, Kazuo Chihara, Katsuzo Fujita, Ikuo KobayashiAbstract:Serum levels of prolactin (PRL), Peptide Histidine methionine (PHM) and vasoactive intestinal Peptide (VIP) were measured in 97 subjects and cerebrospinal fluid (CSF) levels of PHM and VIP were measured in 50 subjects by specific radioimmunoassays to investigate correlations between them. The chromatographic studies revealed that PHM and C-terminal extended form of PHM, Peptide Histidine Valine occurred in human serum and CSF. Significant age-related increases of CSF PHM (P < 0.02) were observed in both males and females, whereas an age-related decrease of serum PRL level was found in females (P < 0.01). In contrast, neither serum VIP, serum PHM nor CSF VIP changed significantly with age. There was a significant positive correlation (P < 0.002) between VIP and PHM in serum, but not in CSF. The close relation between VIP and PHM in serum meets one's expectation because of their derivation from a common precursor. In CSF, these two Peptides did not change in parallel with each other. These results may reflect the alteration in metabolism of PHM in CSF. Finally, there was no correlation between serum PRL concentrations and either serum or CSF levels of the Peptides, suggesting that neither VIP nor PHM levels in CSF as well as in serum can influence the basal PRL secretion in subjects without endocrine disorders.
Billy K. C. Chow - One of the best experts on this subject based on the ideXlab platform.
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Identification of a potential receptor for both Peptide Histidine isoleucine and Peptide Histidine Valine.
Endocrinology, 2002Co-Authors: Dicky Laiyin Tse, Ronald T.k. Pang, Anderson On-lam Wong, Siu-ming Chan, Hubert Vaudry, Billy K. C. ChowAbstract:Peptide Histidine isoleucine (PHI), Peptide Histidine Valine (PHV), and vasoactive intestinal polyPeptide (VIP) are cosynthesized from the same precursor and share high levels of structural similarities with overlapping biological functions. In this study, the first PHI/PHV receptor was isolated and characterized in goldfish. To study this receptor using homologous Peptides, we have also characterized the goldfish prepro-PHI/VIP, and, surprisingly, a shorter transcript lacking the VIP coding region was isolated. A PHI/VIP precursor without the VIP coding sequence has never before been reported. Initial functional expression of the PHI/PHV receptor in Chinese hamster ovary cells revealed that it could be activated by human PHV [50% effective concentration (EC50): 43 nM] and to a lesser extent human PHI (EC50: 133 nM) and helodermin (EC50: 166 nM) but not fish and mammalian pituitary adenylate cyclase-activating polyPeptides and VIPs. Subsequent studies indicated that, similar to the pituitary adenylate cyclase-activating polyPeptide receptors (PAC1-R, VPAC1-R, and VPAC2-R), the receptor isolated in this study is able to interact with goldfish PHI and its C-terminally extended form, PHV with EC50 values 93 and 43 nM, respectively. Northern blot and RT-PCR/Southern blot analyses revealed that the PHI/VIP gene is expressed in the intestine, brain, and gall bladder and the PHI/PHV receptor gene is primarily expressed in the pituitary and to a lesser extend in the intestine and gall bladder, suggesting that PHI/PHV may play a role, notably in the regulation of pituitary function. In conclusion, our results demonstrate for the first time the existence of a PHI/PHV receptor, indicating that the functions of PHI and PHV could be mediated by their own receptor in addition to VIP receptors. (Endocrinology 143: 1327–1336, 2002)