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Biomedical subjects

N Katsube

Publications and source records attributed to N Katsube.

24 records · Page 2Linked to original sources
PubMed1988

New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships.

(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS-411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.

Animals↗
PubMed1986

Atriopeptin turnover: quantitative relationship between in vivo changes in plasma levels and atrial content.

Administration of the 1-deamino-arginine8 vasopressin caused a decrease in right, but not left, atrial levels of atriopeptin (AP) in chloral hydrate-anesthetized rats. The amount of exogenous AP required to match the 1-deamino-arginine8 vasopressin-stimulated plasma levels of AP was equivalent to the decrease in AP content of the right atrium, suggesting that resynthesis of AP did not occur within the 60 min after 1-deamino-arginine8 vasopressin stimulation. The correlation between increased plasma levels and decreased atrial content was also observed in bilaterally nephrectomized rats, suggesting that the kidney is not a major site of degradation of AP in vivo. This finding was confirmed by the comparison of the half-life of exogenous AP in normal (T1/2 = 31 sec) and nephrectomized (T1/2 = 64 sec) animals. Plasma immunoreactivity of the N-terminal fragment of the prohormone (which is also released after cleavage of the precursor peptide) increased 35-fold by 24 hr after nephrectomy in comparison with a 5-fold increase in AP. Half-life studies of the N-terminal fragment suggest that the kidney is the major site of degradation of this molecule. This study demonstrated the different kinetics and renal metabolism of the AP and N-terminal portions of the prohormone.

Animals↗
PubMed1985

Release of atriopeptin in the rat by vasoconstrictors or water immersion correlates with changes in right atrial pressure.

Vasopressin, its 1-deamino analog (dAVP), angiotensin II, and phenylephrine, administered intravenously, increased plasma atriopeptin immunoreactivity in chloral hydrate-anesthetized rats. A continuous one hour infusion of either dAVP or phenylephrine caused a sustained elevation in: a) systemic blood pressure; b) right atrial pressure; c) left ventricular end diastolic pressure; and d) plasma atriopeptin immunoreactivity. While continuous infusion of angiotensin II also produced a sustained elevation in left ventricular end diastolic pressure, the changes in right atrial pressure and plasma atriopeptin were only transient. These data suggest that plasma atriopeptin most closely correlates with right atrial pressure. Consistent with this hypothesis, we found that the release of atriopeptin directly correlated with changes in right atrial pressure in anesthetized, water-immersed rats.

Angiotensin II↗
PubMed1985

Differential structure-activity relationships of atrial peptides as natriuretics and renal vasodilators in the dog.

Natriuretic-diuretic and vasodilator activities of synthetic atriopeptin (AP)-related peptides were examined in the anesthetized dog. We have selected, the naturally occurring, APIII as the reference compound for comparison with various related peptides. APIII is a 24 amino acid peptide with the sequence ser-ser-cys-phe-gly-gly-arg-ile-asp-arg-ile-gly-ala-gln-ser-gly-leu-gly- cys-asn-ser-phe-arg-tyr-OH. APII, another peptide isolated from atrial extracts, lacks the C-terminal arg- of APIII. N-terminal amino acid extensions on APIII or APII, exhibited enhanced natriuretic-diuretic effectiveness. Furthermore, the maximum response obtained by ser-leu-arg-arg-APIII and arg-arg-APIII were significantly higher and the dose-response curve was not parallel to that obtained with APIII. In contrast, there were no significant qualitative or quantitative differences between the renal blood flow responses produced by the N-terminal extended peptides and APII or APIII. These results suggest a heterogeneity of AP receptors in vascular and renal tubular tissues.

Amino Acid Sequence↗