Shouei Kim

Comparison of effects of a potassium channel, opener BRL34915, a specific potassium ionophore valinomycin and calcium channel blockers on endothelin-induced vascular contraction

The effects of a potassium (K+) channel opener BRL34915 and a specific K+ ionophore valinomycin on vasoconstriction induced by endothelin (ET) were compared with those of calcium (Ca2+) channel blockers, nicardipine and verapamil, using helical strips from rat thoracic aorta. ET induced potent and persistent contraction in control solution and similar but smaller contraction in Ca2+-free solution. BRL34915 and valinomycin inhibited the ET-induced contraction dose-dependently in control solution, but not in Ca2+-free solution. The ET-induced contraction was also inhibited by nicardipine and verapamil, though less strongly. On the other hand, high K+ (35 mM)-induced vasoconstriction was strongly inhibited by nicardipine and verapamil, but not by BRL34915 or valinomycin. These results support the idea that the extracellular Ca2+-dependent component of the ET-induced contraction may be mediated by Ca2+ influx by a route other than voltage-dependent Ca2+-channels.

Circulating Levels of Calcitonin Gene-Related Peptide in Patients with Medullary Thyroid Carcinoma

Calcitonin gene-related peptide, originally found in rat medullary thyroid carcinoma cells, was measured by radioimmunoassay in plasma samples with added aprotinin from 17 normal volunteers and 21 patients with medullary thyroid carcinoma. The concentrations were below 75 pmol/l in all 17 normal subjects with a mean of 33 +/- 19 pmol/l plasma. In the patients, the plasma calcitonin gene-related peptide concentrations ranged from below 5 pmol/l to 236 pmol/l, although the mean (36 +/- 48 pmol/l) was not significantly different from the mean normal level. Increase in the plasma calcitonin gene-related peptide level was observed in 2 of 5 patients in response to infusion of 4.3 mg/kg of calcium for 10 minutes and in 3 of 5 patients in response to infusion of 4 micrograms/kg of tetragastrin for 5 minutes. These observations suggest that measurement of calcitonin gene-related peptide level may be helpful in determination of diseases in which the level of calcitonin is of less diagnostic value.

Immunoreactive Parathyroid Hormones in the Circulation and Cerebrospinal Fluid from Patients with Renal Failure

Parathyroid hormone is reported to be a possible causal factor of abnormalities of electroencephalograms of patients with renal failure. In this study, the parathyroid hormone levels were compared in the circulation and cerebrospinal fluid of seven normal subjects and 22 patients with renal failure including those who showed abnormal electroencephalograms. The circulating levels of both C-terminal and N-terminal parathyroid hormone in the subjects studied showed a positive correlation (C-terminal, r = 0.58, P less than 0.01; N-terminal, r = 0.61, P less than 0.01) with the grade of abnormality of the electroencephalogram. However, the levels of C-terminal and N-terminal parathyroid hormone in the cerebrospinal fluid of both normal subjects and patients with renal failure were below the detectable limit (C-terminal, less than 0.1 ng/ml; N-terminal, less than 2.3 pg/ml). These data suggest that in patients with renal failure, the effect of parathyroid hormone on the central nervous system is mediated in some other way than via the cerebrospinal fluid.

ヒトCGRP (Calcitonin gene-related peptide) のRIAの基礎的検討とその臨床応用

Calcitonin gene-related peptide (CGRP) is a peptide recently found by recombinant DNA and molecular biological techniques in rat medullary thyroid carcinoma cells, but its physiological role(s) is unknown. We established a radioimmunoassay for this peptide using human-CGRP (1-37) as a standard, 125I-human-CGRP (1-37) as a tracer, and anti-rat-CGRP (28-37) serum as a first antibody. Aprotinin, an inhibitor of proteolytic enzymes in the plasma, was also added to the assay system, because in its absence the tracer was degraded during incubation with plasma samples. The sensitivity of the assay was 60 pg/ml and the intra- and inter-assay coefficients of variation were 6.0% and 8.5%, respectively. The recovery was 105 +/- 17%. The plasma levels of CGRP in 17 normal subjects (mean +/- S.D. age, 45 +/- 12 years) were all below 300 pg/ml, the mean level being 132 +/- 77 pg/ml. The levels were also below 300 pg/ml in 20 of 21 patients with medullary thyroid carcinoma, but one patient who had a high level of 942 pg/ml (mean value, 142 +/- 193 pg/ml). There was no significant difference between the mean plasma levels of CGRP in normal subjects and patients with medullary thyroid carcinoma. The mean plasma levels of CGRP in 5 patients with medullary thyroid carcinoma did not increase in response to infusion of either 4.3 mg/kg of calcium in 10 minutes or 4 micrograms/kg of tetragastrin in 5 minutes, although the plasma levels of calcitonin in these patients increased markedly during these provocation tests. The levels of CGRP in the cerebrospinal fluid of 16 normal volunteers were all below the detectable limit (less than 60 pg/ml). These findings suggest that fewer patients with medullary thyroid carcinoma than reported previously have high plasma levels of CGRP, either in the basal state or in response to calcium or gastrin, and that the levels of CGRP in the cerebrospinal fluid of normal subjects are very low.