Characterization of the biologically and antigenically important regions of urotensin II.
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Biomedical subjects
Publications and source records attributed to D McMaster.
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In our study alcoholic patients with and without cirrhosis have a decreased serum zinc. They also have increased serum copper and iron with an increase in the serum ferritin. There is no evidence of selenium deficiency in either alcoholic group. Alcohol when given with zinc in a single dose to normal volunteers increases the serum zinc and therefore appears to increase the absorption of zinc.
Serum zinc was measured with and without venous occlusion in 100 subjects. During venous occlusion serum zinc was 0.79 ug/ml and without venous occlusion it was 0.75 ug/ml (p less than 0.001).
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The mean serum zinc in 30 normal volunteers was 12.8 mumol/l (SE +/- 0.3) and in 30 alcoholic subjects was 10.7 mumol/l (SE +/- 0.6) (p less than 0.005). Postprandial changes in serum zinc were studied in these volunteers and alcoholics who were divided into three groups. After a standardized meal with no added zinc there was a sustained postprandial fall in serum zinc in 10 normal volunteers (23%) and in 10 alcoholic subjects (19%). After a standardized meal supplemented with 25 mg zinc there was a similar rise in postprandial serum zinc concentration in 10 alcoholic subjects and 10 normal volunteers. After a standardized meal supplemented with 50 mg zinc there were lower serum zinc concentrations in 10 alcoholic subjects when compared with 10 normal volunteers. These lower postprandial serum zinc concentrations in alcoholics may suggest a reduced absorptive capacity for zinc in alcoholics.
This study reports the characterization of receptors for vasoactive intestinal peptide (VIP) on membranes prepared from bovine cerebral arteries. By use of HPLC we prepared two purified monoiodinated VIP radioligands with nearly equivalent cerebral vasorelaxant potency as native VIP, [Tyr(125I)10 )VIP and [Tyr(125I)22]VIP. The former resulted in a higher proportion of specific binding to arterial membranes than the latter and was therefore thought to be the superior radioligand for receptor characterization. The binding of [Tyr(125I)10]VIP to cerebral arterial membranes was saturable, specific, reversible, and dependent on time and temperature. Scatchard analysis suggested the presence of a high- and a low-affinity binding site with KD values of 0.2 and 11 nM and receptor concentrations of 79 and 737 fmol/mg of protein, respectively. The dose-response curves for binding to the VIP receptor by the VIP-homologous peptides PHI, PHM, and rat growth hormone-releasing factor (GRF) were very similar to their dose-response curves for relaxation of cerebral arteries. The order of potency was VIP greater than PHM greater than PHI greater than rat GRF. It is suggested that the characteristics of the vascular VIP binding sites and the close correlation between the binding and vasorelaxant properties of VIP and its related peptides argue for the vascular binding sites being functional receptors for VIP.
Alcoholism is occasionally complicated by zinc deficiency. We have assessed the possibility that malabsorption of zinc may be a potential cause. Using a dual isotope absorption technique the absorption of 65Zn in 18 alcoholic patients was 37% (13 +/- SD) and 56% (10 +/- SD) in a normal control group (p less than 0.001). The mean serum zinc in 55 alcoholic patients was 11.6 mumol/l (3.0 +/- SD) and in 36 normal volunteers the mean serum zinc was 13.6 mumol/l (1.8 +/- SD; p less than 0.001). This study suggests that chronic alcohol abuse will decrease the absorption of zinc and this may contribute towards the zinc deficiency occasionally associated with alcoholism.
This study has examined changes in gastrointestinal hormones induced by alcohol. Ten normal volunteers consumed an orange and carbohydrate-containing drink on two separate occasions, with and without 50g alcohol. There was a significant hyperglycaemia associated with alcohol ingestion but no difference was noted in insulin or gastric inhibitory polypeptide in the two groups. Gastrin release was stimulated by alcohol but pancreatic polypeptide release and N-terminal glucagon release were both suppressed by alcohol. There was no difference in release of secretin or C-terminal glucagon in either group.
We have studied the vasorelaxant properties of vasoactive intestinal peptide (VIP) using helical strips of bovine, porcine and human brain arteries in vitro. The resting tension of the arterial strips was increased during experiments by prostaglandin F2 alpha or KCl so as to increase the magnitude of the relaxant response to VIP. Arteries supplying different regions of the bovine brain responded potently to VIP with ED50 values of 1.8 nM, 2.3 nM, 6.8 nM and 9.0 nM for the middle, anterior and posterior cerebral arteries and the basilar artery, respectively. The porcine basilar artery and branches of the human middle cerebral artery responded to VIP with ED50 values of 4.2 nM and 1.6 nM, respectively. The homologous neuropeptide, PHI, relaxed the bovine middle cerebral and porcine basilar arteries less potently than did VIP, with ED50 values for PHI being 11 nM and 43 nM, respectively. However, PHI elicited in the two arteries a maximal vasodilatory response of similar magnitude as did VIP. The other homologous peptides, human pancreatic growth hormone releasing factor 1-40 [hpGRF 1-40], secretin, and glucagon, and the VIP fragments, VIP 1-12 and VIP 10-28, were completely inactive. In contrast, VIP, which had been oxidized to VIP-(Met17 sulfoxide) or VIP-(Met17 sulfone), retained full activity. These structure-activity relationships for relaxation of brain arteries are consistent with previous studies of other biological responses to VIP.
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The 41-residue neuropeptide urotensin I (UI), from the urophyses of two teleost fish species (Cyprinus carpio and Catostomus commersoni), was isolated and purified, and its amino acid sequence was determined and confirmed by synthesis of a fully active peptide. The UI peptide was found to be a close structural and biological homologue of the ovine hypothalamic corticotropin-releasing factor (CRF) and the frog skin peptide sauvagine; UI is, therefore, a phylogenetic prototype of this group of peptides. Extraction of urophyses in hot acetic or hydrochloric acid cleaves an amino terminal tripeptide yielding a fully active UI(4-41). The UI peptides are equipotent with the other two naturally occurring peptides (CRF and sauvagine) in the release of mammalian pituitary corticotropin (ACTH), but UI is several times more potent than the mammalian homologue in the stimulation of release of fish pituitary ACTH. The UI peptide and its mammalian or amphibian homologues have a long-lasting hypotensive action in mammals, via a uniquely selective vasodilatation in the superior (anterior) mesenteric vascular bed only. The significantly lower hypotensive vasodilatory action of the mammalian homologue (CRF) suggests a change in the unknown physiological role of the haemodynamic actions of the UI peptides in the mammalian gastrointestinal tract during phylogenetic progression from fishes to mammals.
Serial determinations were carried out on 27 male and 21 female preterm infants (gestational age 28-36 weeks) throughout the first year of life. Serum copper at birth was 0.33 +/- 0.20 micrograms/ml (n equal 8); at 9 weeks, 0.77 +/- 0.19 micrograms/ml (n = 22); at 24 weeks, 1.00 +/- 0.27 micrograms/ml (n = 31), and at 52 weeks 1.21 +/- 0.27 micrograms/ml (n = 40). Serum zinc at birth was 1.03 +/- 0.16 micrograms/ml (n = 9); at 9 weeks, 0.71 +/- 0.11 micrograms/ml (n = 17); at 24 weeks, 1.02 +/- 0.20 micrograms/ml (n = 20), and at 52 weeks, 1.19 +/- 0.34 micrograms/ml (n = 33). The results of this study compare well with values previously reported for infants studied at selected age points.
Urotensin I, purified from extracts of the urophysis of a teleost fish (Catostomus commersoni), exhibits potent hypotensive activity (mammals and birds) and corticotropin-releasing activity (both fish and mammals). The primary structure of this 41-residue peptide was determined to be H-Asn-Asp-Asp-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Asn-Met-Ile-Glu- Met-Ala-Arg-Ile-Glu-Asn-Glu-Arg-Glu-Gln-Ala-Gly-Leu-Asn-Arg-Lys-Tyr-Leu-Asp-Glu -Val-NH2. Extraction with 0.1N HCl at 100 degrees C cleaves the amino-terminal tripeptide, yeilding a fully active analog, urotensin I(4-41). The amino acid sequence was confirmed by measuring the biological activity of synthetic urotensin I(4-41). Urotensin I exhibits a striking sequence homology with ovine corticotropin-releasing factor and with frog sauvagine. These three peptides exhibit similar activities in biological test systems.
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