The effect of arginine vasopressin on endothelin production in the human forearm vascular bed.

OBJECTIVES: To study whether arginine vasopressin (AVP) can stimulate endothelin production and/or release in vivo, in the human forearm vasculature. DESIGN: The effect of the infusion of AVP into the brachial artery on endothelin production across the human forearm vascular bed was studied in healthy male volunteers, and was compared with intra-arterial infusion of placebo. In another group the effects of AVP on endothelin production were studied after a prior infusion of L-NG-monomethyl-arginine (L-NMMA), a nitric oxide-synthase inhibitor. In a fourth group the effect of L-NMMA alone, without AVP infusion, on endothelin production was studied. METHODS: We measured the effects of AVP, placebo, L-NMMA followed by AVP and L-NMMA followed by placebo on arterial and venous endothelin concentrations in the forearm of four groups, each consisting of five healthy male volunteers. Forearm blood flow was measured by strain gauge plethysmography. The endothelin production was calculated as forearm blood flow times (venous - arterial) endothelin concentration. RESULTS: The group infused with L-NMMA followed by infusion of 8 ng AVP/min per dl forearm volume showed a significant rise in endothelin production from 1.3 (1.8) to 5.0 (2.0) pg/min/dl at 15 minutes (p<0.05, ANOVA). This rise in endothelin production was also significantly different from the endothelin production at 15 minutes in the other three groups (p<0.01, ANOVA). CONCLUSION: In healthy male volunteers intra-arterial infusion of AVP induced a rise in endothelin production in the forearm within 15 minutes, but only after prior infusion of L-NMMA. This observation suggests that the AVP-induced production of nitric oxide offsets AVP-mediated release of endothelin.

The gamma-tubulin gene of the malaria parasite Plasmodium falciparum.

By screening of cDNA and genomic libraries of Plasmodium falciparum with a DNA probe derived from the cognate beta-tubulin gene, gene Pf gamma tub has been identified that codes for gamma-tubulin, a newly discovered member of the tubulin superfamily that is indispensible for nuclear division and microtubule assembly [12]. Gene Pf gamma tub is not interrupted by introns and only present as a single-copy in the parasite genome. Its encoded amino acid sequence (452 amino acids; M(r) 50,560) has a 63% similarity to the gamma-tubulins encoded by Aspergillus nidulans, Schizosaccharomyces pombe, Drosophila melanogaster, Xenopus laevis and Homo sapiens. This figure is significantly (approx. 8%) lower than the average identity between the gamma-tubulins of the latter five species suggesting that during evolution the genes have been exposed to different selection pressures. The identity of gamma-tubulin to the Plasmodium falciparum encoded alpha- and beta-tubulins is 30 and 33%, respectively.