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PubMed1990

Persistence of intrinsic neurones and possible phenotypic changes after extrinsic denervation of human respiratory tract by heart-lung transplantation.

Respiratory tract nerves have cell bodies outside (sensory, sympathetic) and inside (parasympathetic) the organ and contain bioactive peptides. These include calcitonin gene-related peptide and tachykinins (sensory nerves), vasoactive intestinal polypeptide (parasympathetic nerves), and neuropeptide with tyrosine (sympathetic nerves). Because transplantation interrupts the extrinsic nerve supply to the tissues, we have examined transplanted human respiratory tracts (n = 11) removed at retransplantation 2 to 42 months after the primary transplant in order to determine whether any nerves and peptide synthesis persist. As controls to establish nerve distribution in human respiratory tract, tissues were obtained from 10 lung resections and five autopsies. Cryostat sections were immunostained to demonstrate the general neural marker PGP 9.5, neuropeptides, and the catecholamine-synthesizing enzyme tyrosine hydroxylase. Nerves immunoreactive for PGP 9.5 were detected in all transplanted tissues. They were fewer in number overall than in control tissue, significantly so in epithelium of trachea and bronchus where they were present sparsely in only three cases. Nerves immunoreactive for tyrosine hydroxylase were significantly fewer in the transplants. Peptide-immunoreactive nerves were also reduced in number in the transplants, except for vasoactive intestinal polypeptide, which was only significantly changed in blood vessels in the lung. Ganglion cells immunoreactive for tyrosine hydroxylase and neuropeptide with tyrosine were seen in the transplanted tissues in five cases, but never in the control tissues. We conclude that whereas some nerves and neuropeptide synthesis persist after extrinsic pulmonary denervation, potentially significant changes also occur, including the appearance in intrinsic parasympathetic neurones of immunoreactivity for a catecholamine-synthesizing enzyme and a peptide normally found in sympathetic nerves.

Adult↗

PubMed1997

Tissue distribution and subcellular localization of rabbit liver metalloendopeptidase.

We have previously isolated rabbit liver microsomal metalloendopeptidase (MEP) as a candidate for the processing enzyme of vitamin K-dependent plasma proteins. A cDNA coding for MEP has revealed that it is structurally related to metalloendopeptidase-24.15, which catalyzes the proteolytic processing of several bioactive peptides. In this study we examined the tissue distribution and subcellular localization of MEP by light and electron microscopic immunohistochemical methods, in addition to Northern blot analysis. Chicken polyclonal antibodies were raised by using synthetic peptides AG1 (Met31-Asn46) and AG3 (Asp537-Gly551) derived from the sequence of MEP. Both anti-AG1 and anti-AG3 antibodies reacted specifically with MEP, as judged by Western blotting and immunohistochemical methods. Both antibodies gave an identical staining distribution, which was localized on the luminal cell surfaces and in the cytoplasm of the following organs: liver, brain, lungs, kidneys, esophagus, stomach, duodenum, pancreas, placenta, epididymis, uterus, ovary, and oviduct. Northern blot analysis revealed that the expression of MEP mRNA is similar to its immunohistochemical distribution except in the heart. These results suggest that MEP may participate more closely in a degradation role in peptide metabolism in various tissues than in a processing role of the proprotein, like metalloendopeptidase-24.15.

Amino Acid Sequence↗

PubMedDate not supplied

What is the future of diabetic wound care?

With diabetes affecting 5% to 10% of the US population, development of a more effective treatment for chronic diabetic wounds is imperative. Clinically, the current treatment in topical wound management includes debridement, topical antibiotics, and a state-of-the-art topical dressing. State-of-the-art dressings are a multi-layer system that can include a collagen cellulose substrate, neonatal foreskin fibroblasts, growth factor containing cream, and a silicone sheet covering for moisture control. Wound healing time can be up to 20 weeks. The future of diabetic wound healing lies in the development of more effective artificial "smart" matrix skin substitutes. This review article will highlight the need for novel smart matrix therapies. These smart matrices will release a multitude of growth factors, cytokines, and bioactive peptide fragments in a temporally and spatially specific, event-driven manner. This timed and focal release of cytokines, enzymes, and pharmacological agents should promote optimal tissue regeneration and repair of full-thickness wounds. Development of these kinds of therapies will require multidisciplinary translational research teams. This review article outlines how current advances in proteomics and genomics can be incorporated into a multidisciplinary translational research approach for developing novel smart matrix dressings for ulcer treatment. With the recognition that the research approach will require both time and money, the best treatment approach is the prevention of diabetic ulcers through better foot care, education, and glycemic control.

Diabetes Complications↗

PubMed2003

Ceramic drug delivery: a perspective.

Different ceramic substances are offered in the market as bone substitute materials. These include monophasic calcium phosphate ceramics of tricalciumphosphate (TCP) or hydroxyapatite (HA), biphasic calcium phosphate ceramics and multiphasic bio-glasses synthetic calcium phosphate cements. Ceramics with appropriate three-dimensional geometry are able to bind and concentrate bone morphogenetic proteins in circulation and may become osteoinductive (capable of osteogenesis) and can be effective carriers of bioactive peptide or bone cell seeds and are therefore potentially useful in tissue engineering and drug delivery. An attempt has been made to review various drug delivery applications of ceramics.

Biocompatible Materials↗

PubMed2005

Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor system.

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has shed new light on the neurobiology of sleep/wakefulness regulation and anxiety-like behavior. NPS can potently promote arousal and suppress all stages of sleep. This effect might be modulated by NPS receptors expressed in thalamic centers that are relays for transmitting arousing stimuli originating from the brainstem to the cortex. The peptide precursor is expressed most prominently in a novel nucleus located directly adjacent to the noradrenergic locus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. This unique pharmacological profile of NPS offers significant potential for developing new drugs for the treatment of sleep and/or anxiety disorders.

Animals↗

PubMed2006

Inhibition of dipeptidyl-peptidase IV does not increase circulating IGF-1 concentrations in growing pigs.

The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. Pigs were administered either sterile saline (0.11 ml/kg followed by a continuous infusion at 2 ml/hr for 72 hrs, controls, n = 2), Compound 1 (2.78 mg/kg followed by a continuous infusion at 0.327 mg/kg x hr for 72 hrs, n = 4) or GHRH (0.11 ml/kg sterile saline, followed by a continuous infusion of GHRH at 2.5 microg/ kg x hr for 48 hrs, n = 4). Plasma concentrations of Compound 1 were maintained at 1 microM, which resulted in a 90% inhibition of circulating DPP-IV activity. Relative to the predose 24-hr period, area under the IGF-1 concentration curve (AUC) tended to be lower (P = 0.062) with Compound 1 (.79 +/- 130 ng/ml x hr) than controls (543 +/- 330 ng/ml x hr). GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. Compound 1). We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig.

Animals↗

PubMed1987

Autoradiographic localization of dihydrotestosterone binding in the major salivary glands and other androgen-responsive organs of the mouse.

Mouse submandibular glands show an androgen-dependent sexual dimorphism, reflected in higher concentrations in males than in females of bioactive peptides, such as epidermal growth factor (EGF), nerve growth factor, and renin in the cells of the granular convoluted tubules (GCT). Biochemical studies have demonstrated androgen receptors in submandibular gland and other androgen-responsive organs in mouse. We have determined the cellular localization of these receptors using steroid autoradiography. Fifteen adult gonadectomized male mice were injected intravenously with 0.13 microgram or 0.26 microgram [3H]-dihydrotestosterone (SA 135 Ci/mM); some animals were pre-treated with cyclocytidine to stimulate secretion by GCT cells. Animals were killed 15 min, 1, 2, or 3 hr after isotope injection. Steroid autoradiographs were prepared, and some were stained immunocytochemically for EGF. Of the different cell types of submandibular gland, the acinar cells most frequently and intensely concentrated [3H]-DHT; GCT cells also concentrated the hormone, as did a small number of striated duct cells. In the other major salivary glands, the only cells that concentrated the androgen were interlobular striated duct cells in sublingual gland. In prostate, anterior pituitary, and brain a large number of cells concentrated androgen, as has been previously reported. Androgen binding by the GCT cells was a predictable finding, since androgen-induced alterations in composition and form of these cells are well documented. The intense androgen concentration by the acinar cells was an unexpected finding and suggests a hitherto unknown androgen regulation of these cells. An incidental finding was intense concentration of [3H]-DHT in the nuclei of the endothelial cells of the post-capillary venules of the cervical lymph nodes.

Animals↗

PubMed2005

Stromal mesenchyme cell genes of the human prostate and bladder.

BACKGROUND: Stromal mesenchyme cells play an important role in epithelial differentiation and likely in cancer as well. Induction of epithelial differentiation is organ-specific, and the genes responsible could be identified through a comparative genomic analysis of the stromal cells from two different organs. These genes might be aberrantly expressed in cancer since cancer could be viewed as due to a defect in stromal signaling. We propose to identify the prostate stromal genes by analysis of differentially expressed genes between prostate and bladder stromal cells, and to examine their expression in prostate cancer. METHODS: Immunohistochemistry using antibodies to cluster designation (CD) cell surface antigens was first used to characterize the stromas of the prostate and bladder. Stromal cells were prepared from either prostate or bladder tissue for cell culture. RNA was isolated from the cultured cells and analyzed by DNA microarrays. Expression of candidate genes in normal prostate and prostate cancer was examined by RT-PCR. RESULTS: The bladder stroma was phenotypically different from that of the prostate. Most notable was the presence of a layer of CD13+ cells adjacent to the urothelium. This structural feature was also seen in the mouse bladder. The prostate stroma was uniformly CD13-. A number of differentially expressed genes between prostate and bladder stromal cells were identified. One prostate gene, proenkephalin (PENK), was of interest because it encodes a hormone. Secreted proteins such as hormones and bioactive peptides are known to mediate cell-cell signaling. Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis. Gene expression analysis showed that PENK expression was down-regulated in prostate cancer. CONCLUSION: Our findings show that the histologically similar stromas of the prostate and bladder are phenotypically different, and express organ-specific genes. The importance of these genes in epithelial development is suggested by their abnormal expression in cancer. Among the candidates is the hormone PENK and the down-regulation of PENK expression in cancer suggests a possible association with cancer development.

Cells, Cultured↗

PubMed2003

Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function.

Recruitment and activation of leukocytes are important for elimination of microbes, including viruses, from infected areas. Chemokines constitute a group of bioactive peptides that regulate leukocyte migration and also contribute to activation of these cells. Chemokines are essential mediators of inflammation and important for control of viral infections. The profile of chemokine expression contributes to shaping the immune response during viral infection, whereas viral subversion of the chemokine system allows the virus to evade antiviral activities of the host. In this review, we discuss the role of chemokines in host-defense against virus infections, and we also look deeper into the virus-cell interactions that trigger chemokine expression as well as the cellular signaling cascades involved.

Animals↗

PubMed1984

Physiological functions of glucocorticoids in stress and their relation to pharmacological actions.

Almost any kind of threat to homeostasis or stress will cause plasma glucocorticoid levels to rise. The increased levels have traditionally been ascribed the physiological function of enhancing the organism's resistance to stress, a role well recognized in glucocorticoid therapy. How the known physiological and pharmacological effects of glucocorticoids might accomplish this function, however, remains a mystery. A generalization that is beginning to emerge is that many of these effects may be secondary to modulation by glucocorticoids of the actions of numerous intercellular mediators, including established hormones, prostaglandins and other arachidonic acid metabolites, certain secreted neutral proteinases, lymphokines, and a variety of bioactive peptides. These mediators participate in physiological mechanisms--endocrine, renal, immune, neural, etc.--that mount a first line of defense against such challenges to homeostasis as hemorrhage, metabolic disturbances, infection, anxiety, and others. Contrary to the traditional view that glucocorticoids enhance these defense mechanisms, however, it has become increasingly clear that glucocorticoids at moderate to high levels generally suppress them. This paradox, which first emerged when glucocorticoids were discovered to be antiinflammatory agents, remains a major obstacle to a unified picture of glucocorticoid function. We propose that stress-induced increases in glucocorticoid levels protect not against the source of stress itself but rather against the body's normal reactions to stress, preventing those reactions from overshooting and themselves threatening homeostasis. This hypothesis, the seeds of which are to be found in many discussions of particular glucocorticoid effects, immediately accounts for the paradox noted above. Furthermore, it provides glucocorticoid physiology with a unified conceptual framework that can accommodate such apparently unrelated physiological and pharmacological effects as those on carbohydrate metabolism, inflammatory processes, shock, and water balance. It also leads us to suggest that some of the enzymes rapidly induced by glucocorticoids, such as glutamine synthetase, detoxify mediators released during stress-induced activation of primary defense mechanisms. These mediators would themselves lead to tissue damage if left unchecked.

Animals↗

PubMed2003

Effect of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide on mouse preantral follicle development in vitro.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide isolated from ovine hypothalamus. It is transiently expressed in preovulatory follicles and positively affects several parameters correlated with the ovulatory process. It has also been shown to be expressed in the interstitial tissue around primordial and preantral follicles. The aim of the present study was to investigate whether PACAP influences preantral follicle growth and differentiation. Mouse preantral follicles were cultured for 5 d in the presence of FSH and increasing concentrations of PACAP or vasoactive intestinal polypeptide (VIP) (10(-12) to 10(-7) m). In the presence of FSH, follicles increased in diameter and formed an antrum. At the concentrations tested, neither PACAP alone nor VIP alone had any effect on follicle development, but the addition of either peptide to FSH-stimulated follicles caused a dose-dependent inhibition of follicle growth, antrum formation, granulosa cell proliferation, and estradiol production. The effect of PACAP on follicle growth and antrum formation was directly correlated with the length of stimulation and was reversible. Although exposure of follicles to 10(-7) m PACAP and VIP did not affect oocyte growth, it severely impaired completion of meiotic maturation in oocytes isolated from the follicles and cultured for 17 h in medium alone. The cyclic production of PACAP by preovulatory follicles during the estrous cycle in adult rats and its induction by LH in the rat and mouse ovary suggest that this peptide may play a role in the local regulation of preantral follicle growth.

Animals↗

PubMed2006

Effects of obestatin on energy balance and growth hormone secretion in rodents.

Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its biological activity and acts through the orphan receptor, GPR-39. Obestatin was shown to have actions opposite to ghrelin on food intake, BW, and gastric emptying. In the present study, we failed to observe any effect of obestatin on food intake, BW, body composition, energy expenditure, locomotor activity, respiratory quotient, or hypothalamic neuropeptides involved in energy balance regulation. In agreement with the first report, we were unable to find any effect of obestatin on GH secretion in vivo. Moreover, we were unable to find mRNA expression of GPR-39, the putative obestatin receptor, in the hypothalamus of rats. Therefore, the results presented here do not support a role of the obestatin/GPR-39 system in the regulation of energy balance.

Animals↗

PubMed1985

Peptidyl-glycine alpha-amidation activity in tissues and serum of the adult rat.

Bioactive peptides frequently terminate in a carboxyl-terminal alpha-amide. The tissue distribution of enzymatic activity capable of converting [125I]D-Tyr-Val-Gly into [125I]D-Tyr-Val-NH2 has been determined. Assay conditions have been established so that enzyme activity can be measured in crude homogenates. In adult male rats, the highest concentrations of activity are found in the anterior and neurointermediate lobes of the pituitary. Lower concentrations of activity are found in the hypothalamus, submandibular glands, and the rest of the brain. Enzyme activity is also easily assayed in serum. Taking into account the mass of each tissue, the submandibular glands and the brain are the major tissue sources of enzymatic activity; serum contains more enzymatic activity than is found in the pituitary gland. In all tissues and in serum, enzyme activity is stimulated by the addition of copper sulfate and ascorbate and is dependent on molecular oxygen. This activity is, therefore, referred to as peptidyl glycine alpha-amidating monooxygenase (PAM) activity. The pH optima for PAM activity in the pituitary and submandibular glands are near neutrality, whereas the pH optima for PAM activity in serum and hypothalamus are broad, with substantial activity at alkaline pH.

Animals↗

PubMed1990

Prolactin proteolysis by glandular kallikrein: in vitro reaction requirements and cleavage sites, and detection of processed prolactin in vivo.

Glandular kallikrein (GK) is a trypsin-like serine protease characterized by an ability to generate bioactive peptides from inactive precursors with high specificity. In rat pituitary lactotrophs, GK is an estrogen-induced dopamine-repressed protein which is coregulated with PRL and is localized in organelles associated with precursor processing, suggesting a function to process PRL to novel forms with unique biological activities. To investigate this hypothesis we studied the ability of GK to cleave PRL in vitro and also examined rat pituitary extracts for processed forms of PRL using Western blot analysis. GK did not cleave rat PRL under routine incubation conditions. However, GK converted PRL from a 25K form to a 22K form (by gel electrophoresis) in the presence of thiols (dithiothreitol or mercaptoethanol) and Triton X-100. These reagents appear to elicit proteolysis by altering PRL's conformation; thiols were essential for proteolysis and Triton X-100 enhanced the thiol effects. Sequencing of processed PRL revealed 3 cleavage sites: Arg174-Arg175,Lys185-Phe186, and Arg188-Cys189. The cleavage sites are clustered close to the C-terminus on a 16-amino acid domain bracketed by cysteine residues. The cleavage sites in PRL resemble those of other GK substrates in their structural features and are in a highly conserved domain of PRL. Western blot analysis of rat pituitary extracts using antiserum against rat PRL revealed 22K PRL variants that were highly estrogen dependent and whose levels were markedly increased by in vivo administration of cysteamine, a biological thiol known to alter pituitary PRL conformation in vivo. The 22K PRL variants comigrated with PRL bands generated by sequential in vitro processing with GK and carboxypeptidase-B. The present findings support the hypothesis that GK may function to process PRL to novel forms in rat lactotrophs.

Amino Acid Sequence↗

PubMed2003

Enhancement of aminopeptidase A expression during angiotensin II-induced choriocarcinoma cell proliferation through AT1 receptor involving protein kinase C- and mitogen-activated protein kinase-dependent signaling pathway.

Angiotensin II (Ang II) is a bioactive peptide of the renin-angiotensin system, exerting its actions not only as a vasoconstrictor, but also as a growth promoter. In human placenta, type 1 Ang II receptors (AT(1)R) are predominantly expressed in trophoblasts, and we previously reported that aminopeptidase A (APA), a cell surface peptidase that converts Ang II to Ang III, is also expressed in both normal and neoplastic trophoblasts. However, the roles of Ang II and APA in trophoblast function remain to be clarified. In the present study we examined the effects of Ang II on proliferation and APA expression in trophoblast-like BeWo choriocarcinoma cells. Treatment of BeWo cells with Ang II significantly increased DNA synthesis in a dose-dependent manner. Ang II also enhanced APA mRNA and cell surface expression in BeWo cells analyzed by Northern blotting, flow cytometry, and enzyme activity assay. The Ang II-induced proliferation and APA up-regulation were blocked by the AT(1)R antagonist candesartan, but not by the AT(2)R antagonist PD123319. Furthermore, these Ang II effects were abolished by the protein kinase C inhibitor bisindolylmaleimide I and the MAPK inhibitor PD98059. Immunohistochemistry using choriocarcinoma tissues demonstrated that APA was expressed on the cell surface of AT(1)R-positive cytotrophoblastic cells in vivo. With these findings we demonstrate that Ang II stimulates the proliferation of trophoblastic cells via AT(1)R that are linked to protein kinase C /MAPK-dependent signaling pathways, and that the Ang II-degrading enzyme APA is up-regulated during Ang II-induced cell proliferation. These observations suggest the possible regulatory mechanism by the local renin-angiotensin system, especially the Ang II-AT(1)R-APA system, for the growth of human choriocarcinoma cells.

Aminopeptidases↗

PubMed1993

Cellular localization of membrane metalloendopeptidase (enkephalinase) in human endometrium during the ovarian cycle.

Previously, we found that membrane metalloendopeptidase (MMEP; enkephalinase) is present in human endometrium where it may inactivate certain bioactive peptides such as endothelin. The specific activity of MMEP in endometrium is correlated positively with the level of plasma progesterone. In the present study, we determined the cellular distribution of MMEP immunoreactivity (IR) in samples of endometrium from 31 ovulatory women at different phases of the menstrual cycle and from 5 postmenopausal women. At all times, MMEP-IR was localized in the endometrial stromal cells and was absent from myometrium, epithelia, and vessels. The presence of the enzyme on the stromal cell plasma membrane was demonstrated by immunostaining of freshly isolated endometrial stromal cells. During the endometrial cycle, there were dramatic changes in MMEP-IR in the zona functionalis: In the proliferative phase when plasma progesterone levels were low, MMEP-IR was weak; but after ovulation, during the early and midsecretory phases, when progesterone levels were increasing or high, MMEP-IR was strong. During the late secretory phase, in the stromal areas that were decidualized, contiguous with spiral arterioles and beneath the surface epithelium, most of the MMEP-IR was lost, whereas MMEP in the other stromal areas remained strong. In the premenstrual phase, there was a more generalized decline in MMEP-IR in the stromal cells. MMEP-IR in the zona basalis was weak to moderate and was relatively unchanged during the ovarian cycle; the findings in postmenopausal tissues were similar to those of proliferative phase tissues. These results are consistent with the previous findings of increased MMEP mRNA, protein, and activity in endometrial tissue of midsecretory phase and in cultured endometrial stromal cells in response to progestin. Furthermore, in this study, we demonstrate that in the late secretory phase in decidualizing stroma, MMEP-IR is decreased considerably compared with midsecretory stromal cells. These changes in MMEP-IR are consistent with the possibility that endothelin, also produced in endometrium, is spared inactivation in the premenstrual phase and may act on the spiral arterioles. These findings are supportive of a role for MMEP in paracrine interactions affecting vascular homeostasis in the endometrium.

Endometrium↗

PubMed1994

A high abundance midregion species of parathyroid hormone-related protein: immunological and chromatographic characterization in plasma.

The widespread expression of the gene for PTH-related protein (PTHrP) and the high interspecies conservation of the primary sequence of even the non-PTH-like portion of the protein argue for a vital role(s) for PTHrP in normal physiology. Emerging evidence suggests that PTHrP may be processed into smaller bioactive peptides, but the circulating forms of PTHrP are not well characterized. We have measured plasma concentrations in well defined patient groups using a RIA directed toward midregion PTHrP-(37-74), compared midregion concentrations to amino-terminal and carboxy-terminal PTHrP concentrations in the same patients, and further defined the components of midregion PTHrP immunoreactivity by high pressure liquid chromatography. Patients with humoral hypercalcemia of malignancy (HHM) had concentrations of PTHrP-(37-74) immunoreactivity of 90 +/- 10 pmol/L (mean +/- SEM), 9-fold higher than PTHrP-(1-74) immunoreactivity and about 3-fold higher than PTHrP-(109-138) immunoactivity. There was no consistent elevation of midregion PTHrP in patients with local osteolytic hypercalcemia, hyperparathyroidism, or renal failure, but discrimination of these groups from HHM was less complete using PTHrP-(37-74) than using PTHrP-(1-74) immunoactivity. By reverse phase high pressure liquid chromatography, plasma PTHrP-(37-74) immunoactivity in patients with HHM was resolved into three components: 1) a major peak coeluting with that found in medium conditioned by cells transfected with human PTHrP-(1-141), which we have previously sequenced and found to represent a midregion peptide beginning at residue 38; 2) a minor peak with both PTHrP-(37-74) and -(1-74) immunoreactivity; and 3) another minor peak with PTHrP-(37-74), but not PTHrP-(1-74), immunoactivity. In conclusion, the predominant circulating form of PTHrP in patients with HHM is a midregion species similar or identical to the peptide beginning at residue 38, which has been shown to be a secretory form of PTHrP.

Adult↗

PubMed1996

Plasma adrenomedullin concentration in patients with heart failure.

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.

Adrenomedullin↗