Interaction of prostaglandin E2 and β-adrenergic catecholamines in the regulation of uterine smooth muscle motility and adenylate cyclase in the rat

Abstract

Prostaglandin E₂ (PGE₂) increased the force of the spontaneous contractions of the rat myometrium and decreased the sensitivity of the uterus to the relaxing effects of the specific β-adrenergic catecholamine agonist isoprenaline. Prostaglandin E₂, at concentrations above 10 μmol/l, increased cyclic AMP production by intact muscle strips. The muscle strips were far more sensitive, however, to the inhibitory effect PGE₂ had on isoprenaline-dependent cyclic AMP production (threshold 2 and isoprenaline stimulated adenylate cyclase activity of a myometrial subcellular (particulate) fraction in a guanyl nucleotide-requiring manner. When present in saturating concentrations (100 μmol/l), the stimulatory effects were not additive, suggesting that the receptors for the two agonists competed for the same catalytic subunit of adenylate cyclase or for the same guanyl nucleotide-requiring factor which couples receptors and enzyme. If muscle strips were incubated with PGE₂ before the preparation of the adenylate cyclase-containing particulate fraction, the enzyme became less responsive to stimulation by guanyl nucleotide and by isoprenaline and PGE₂ in the presence of guanyl nucleotide. The PGE₂ receptor may therefore interact with the β-adrenoreceptor to inhibit isoprenaline-dependent cyclic AMP production by intact muscle cells by desensitizing adenylate cyclase, possibly at the level of the guanyl nucleotide-dependent coupling step. J. Endocr. (1984) 102, 329–336