We investigated the effect of translational suppression of m-calpain on [3H]-phosphatidylcholine (PC) secretion utilising an antisense oligodexoyribonucleotide (oligo) directed against mRNA encoding m-calpain catalytic subunit. Two types of oligo, sense (S) and antisense (AS), to a portion of exon 12 of rat m-calpain catalytic subunit mRNA were tested. Constitutive secretion was decreased by 23% by AS-oligo (1 microM) treatment, while S-oligo (1 microM) had no effect. TPA-stimulated secretion was inhibited about 50-60% by AS-oligo (1-3 microM) and the inhibition was concentration-dependent, while S-oligo (1 microM) only inhibited about 10% of TPA-stimulated secretion. Northern and Western blot analyses revealed that the AS-oligo treatment reduced m-calpain mRNA and protein levels by 32% and 78%, respectively. The data indicate that antisense strategy is effective in suppressing calpain expression and type II cell secretion.