Functionally differentiating two neuronal nitric oxide synthase isoforms through antisense mapping: evidence for opposing NO actions on morphine analgesia and tolerance.

ABSTRACT: Several isoforms of neuronal nitric oxide synthase (nNOS) have been identified. Antisense approaches have been developed which can selectively down-regulate nNOS-1, which corresponds to the full-length nNOS originally cloned from the brain, and nNOS-2, a truncated form lacking two exons which is generated by alternative splicing, as demonstrated by decreases in mRNA levels. Antisense treatment also lowers nNOS enzymatic activity. Down-regulation of nNOS-1 prevents the development of morphine tolerance. Whereas morphine analgesia is lost in control and mismatch-treated mice given daily morphine injections for 5 days, mice treated with antisense probes targeting nNOS-1 show no decrease in their morphine sensitivity over the same time period. Conversely, an antisense probe selectively targeti

SUBMITTER: Kolesnikov YA 

PROVIDER: S-EPMC21584 | biostudies-literature | 1997 Jul

REPOSITORIES: biostudies-literature