Two analytical methods, radioreceptor assay and radioimmunoassay, for the determination of dihydroergotoxine have been developed. Antiserum, providing sufficient sensitivity for the radioimmunoassay, was produced by immunizing rabbits with D-lysergic acid coupled to bovine serum albumin. Radioreceptor assay utilizing dopamine receptor was carried out to determine dihydroergotoxine and its pharmacologically active metabolites in rabbit plasma, and the result was compared with that obtained by radioimmunoassay. The values obtained in both assays were almost identical; it was, therefore, assumed that the plasma concentrations of dihydroergotoxine determined by the present radioimmunoassay reflects the amount of unchanged drug and its active metabolites.

Animals↗

PubMed1983

GDP does not support activation of adenylate cyclase nor ADP-ribosylation of a guanine nucleotide binding protein by cholera toxin.

The actions of cholera toxin (i.e., activation of adenylate cyclase and ADP-ribosylation of a guanine nucleotide binding protein in purified membranes from rat liver) were GTP dependent. Neither of these actions of cholera toxin was reproduced with GDP. Simultaneous addition of ATP and MgCl2 along with GDP allowed cholera toxin to exert these actions. The role of GDP in adenylate cyclase regulation was discussed.

Adenosine Diphosphate Ribose↗

PubMed1983

GDP does not mediate but rather inhibits hormonal signal to adenylate cyclase.

This study was aimed to elucidate whether GDP can mediate hormonal signal to adenylate cyclase in hepatic glucagon sensitive adenylate cyclase with ATP as substrate. Conversion of added GDP to GTP catalyzed by nucleoside diphosphate kinase was suppressed to less than 0.3% of added GDP by including UDP. Inhibition of this enzyme activity by UDP was accompanied by a preferential loss of the stimulatory effect of glucagon plus GDP on cyclase activity without changes in effects of glucagon plus GTP, glucagon plus guanosine 5'-(beta, gamma-imino)triphosphate, and NaF. Under this condition, i.e. in the presence of UDP, GDP competitively inhibited the actions of GTP (Ki for GDP, 1 microM) and guanosine 5'-(beta, gamma-imino)triphosphate in the presence of glucagon, the inhibition being complete at high GDP concentrations. GDP also inhibited cyclase activity stimulated by NaF with UDP but did only slightly without UDP. It was demonstrated that nucleoside diphosphate kinase is located in membranes in addition to cytosol fraction. However, the activity of membrane-associated enzyme was not affected by the addition of glucagon. Based on these observations, it is concluded that GDP is unable to mediate hormonal signal to adenylate cyclase and that it acts as an inhibitor of cyclase activity stimulated by GTP or its analog along with hormone. The results suggest a possible role of membrane-associated nucleoside diphosphate kinase in determining GTP and GDP levels at or near their binding site so as to replenish GTP and, thereby, decrease the inhibitory action of GDP when hormone is present.

Adenylyl Cyclases↗

PubMed1983

Bilateral intracranial granulomas as a complication of infected subdural peritoneal shunt.

Intracranial granuloma in childhood is considered to be a very rare disorder. A three-year-old child is described who had bilateral intracranial granulomas originating from the ends of bilateral subdural-peritoneal shunts. Serial computerized tomographic examinations revealed variable and peculiar findings. Since subdural-peritoneal shunt is used in neonate, intracranial granuloma must be considered as a potential complication of unremoved subdural-peritoneal shunt.

Brain Diseases↗

PubMed1983