DNA antisense strategies in the study of receptors for vasoactive peptides, and of growth and wound-healing factors.
Antisense oligodeoxynucleotide technology has contributed greatly to the overall understanding of both mRNA stability as well as translational processes leading to protein synthesis. Arrest of translational processes by DNA antisense strands usually reduces maximal effects of agonists without affecting their apparent affinities in treated isolated vascular or nonvascular preparations. In the present study, examples are given of DNA antisense oligonucleotide-induced repression of receptors for endothelins, kinins as well as of the platelet-derived growth factor. Furthermore, the efficiency of this technology illustrates the roles of protooncogenes (c-myc and c-myb) in wound-healing mechanisms. The overall mechanism of action of these oligomers is described and the relevance of size, chemical alterations and mode of delivery are illustrated. Release of oligophosphorothioates from polymer matrices and gels can produce a prolonged effect in vivo. Antisense oligonucleotides remain essential in experimental models for which receptor antagonists or selective inhibitors of intracellular components are currently unavailable.
D'Orléans-Juste
P
P
Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Québec, Canada.
Sirois
M G
MG
Edelman
E R
ER
Regoli
D
D
Pheng
L H
LH
Bkaily
G
G
Lindsey
C J
CJ
D000818:Animals; D016232:Endothelins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005821:Genetic Techniques; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007705:Kinins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D014945:Wound Healing / Q000187:drug effects*
D016232:Endothelins; D006133:Growth Substances; D007705:Kinins; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D018000:Receptors, Peptide