The effect of M&B 22948 on carbachol-induced inositol triphosphate accumulation and contraction in iris sphincter smooth muscle

Abstract

The effect of a cyclic GMP phosphodiesterase inhibitor, M&B 22948, on carbachol-induced phosphatidylinositol 4,5-bis-phosphate (PIP 2) breakdown and phosphatidic acid labeling, 1,4,5-inositol triphosphate (IP 3) accumulation and muscle contraction was studied in bovine iris sphincter smooth muscle. Addition of carbachol (10 μM) to 32P-labeled tissue resulted in increased labeling of phosphatidic acid and hydrolysis of PIP 2. In myo[ 3H]inositol labeled tissue, carbachol caused rapid accumulation of IP 3 which reached its maximum at about 2 min. Under identical experimental conditions, carbachol initiated a rapid increase in muscle contraction (phasic component) which was followed by a slightly lower contractile response (tonic component) that lasted for several minutes. Pretreatment of the iris sphincter with M&B 22948 did not alter carbachol-stimulated PIP 2 breakdown and phosphatidic acid labeling, IP 3 accumulation, or phasic component of the contractile response. However, the tonic component of the contractile response was increasingly attenuated by increasing concentrations of the drug. In conclusion, the data presented demonstrate a close correlation between carbachol-induced IP 3 accumulation and muscle contraction, and that M&B 22948 does not inhibit carbachol-induced responses in the iris sphincter.