Species differences in the effects of leukotrience D 4 on inositol trisphosphate accumulation, cyclic AMP formation and contraction in irs sphincter of the mammalian eye

Abstract

The effects of leukotriene (LT) D 4 on inositol trisphosphate (IP 3) accumulation, cAMP formation, and contraction in the iris sphincter smooth muscle of different mammalian species were investigated and functional and biochemical reciprocal interactions between the IP 3Ca 2+ and cAMP second messenge systems were demonstrated. The effects of the LT on the biochemical and pharmacological responses are dose- and time-dependent, and are not mediated through the release of acetylcholine or prostaglandins. Addition of LTD 4 (0.1–1 μM) to cat and bovine iris sphincteris increased IP 3 accumulation by 60% of that of the control and induced muscle contraction (the EC 50 value for the contractile response in the cat sphincter was 4.8 × 10 −9 M), but had no effect on cAMP formation in these species. In contrast, addition of LTD 4 to dog, human, pig, and rabbit sphincters increased cAMP formation by 53–% of their respective controls, but had no effect on IP 3 accumulation and on the contractile state. The rates of formation of LTs in irus sphincters of the different species were found to increse in the following order: bovine < cat < human < dog < pig < rabbit. This could suggest that desensitization of LT receptors may in part underlie the species differences observed in the effects of LTD 4. We suggest that LTD 4 may be involved in regulation of contraction and relaxation in the iris sphincter by increasing IP 3 accumulation and consequently Ca 2+ mobilization and muscle contraction, and by elevating the level of cAMP which in turn may be involved in the regulation of muscle tension.