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Analysis of the functions of the amino acids in the transmembrane segment 6 of human P-glycoprotein during drug transport by using mutant cDNAs expressed in mouse NIH 3T3 cells reveals that four distinct mutations regulate the substrate specificity and the resistance to cytotoxin drugs of P-glycoprotein. Mutant Val338 to Ala increases resistance to colchicine and decreases that to vinblastine, while mutant Gly341 to Val induces little resistance to doxorubicin or colchicine. Mutant Ala342 to Leu decreases the resistance of the P-glycoprotein to all the three drugs, while mutant Ser344 to Cys, Thr, Ala or Tyr completely eliminates the drug resistance.

Na(+)/Ca(2+) exchanger DNA, separated from human embryonic kidney cell line (HEK 293), is similar to an alternatively united human kidney isoform. Endogenous Na(+)/Ca(2+) exchanger expression is low in HEK 293 cell line. Recombinant baculovirus facilitates the high expression of human kidney Na(+)/Ca(2+) exchanger isoform in insect cells.

An analysis of the interaction of rat renal P-glycoprotein with drugs and a hydrophobic element in rat urine reveals that the capacity of several drugs for high affinity binding to P-glycoprotein makes possible their inhibition of urinary excretion of an endogenous substrate. The transport role in kidney and a possible function in drug secretion and drug-induced nephrotoxicity are examined.

A study was conducted to identify and characterize rat cDNAs encoding possible mammalian homologues of the yeast secretory pathway Ca2+ pump. mRNAs corresponding to the cDNA were observed in all subject tissues which indicates mRNA's housekeeping function. Further comparative analyses supported the hypothesis that the alternatively spliced mRNAs are mammalian homologues of the yeast secretory pathway calcium pump.

To understand the role of symptom attribution in treatment-seeking behaviours, survey results of 1356 veterans (age = 38–72 years) were analysed. Controlling for symptom frequency, significant relationships were found for specialist and psychological-related consultations. Those who favoured psychological explanations for symptoms were more likely to attend specialist and psychology-related consultations and filled significantly more prescriptions than people who predominantly explained symptoms by situational factors (normalisers). Veterans who favoured somatic explanations attended more general practitioner consultations than normalisers. Attributional style should be considered part of the constellation of factors influencing healthcare usage. Normalisers, the predominant group, used fewest health services and filled fewest prescriptions; this may have important implications for healthcare considering their tendency to minimise or downplay symptoms. [ABSTRACT FROM AUTHOR]

A study was conducted to examine the effect of correctors and the [Delta]F508 mutation on interactions between the halves of cystic fibrosis transmembrane conductance regulator (CFTR) when expressed as separate polypeptides. The cross-linking of mutant [Delta]F508/NBD1(V510C)/TMD2(A1067C) restored by the correctors NBD1 and TMD2 indicated that the correctors promoted proper interactions between the two halves of CFTR.

The changes in the transmembrane (TM) segments caused by human P-glycoprotein were examined. Catalytic carboxylate mutations were introduced into double cysteine mutants that exhibited ATP dependent cross linking and it was found that ATP alone cloud change disulfide cross-linking between TM segments.

Cysteine-scanning mutagenesis and oxidative cross-linking is used to test for changes in the packing of TM 11 during ATP hydrolysis. The results indicate that rearrangement of TM11 might contribute to the release of drug substrate during ATP hydrolysis.