PROSTAGLANDINS FACILITATE PEPTIDE RELEASE FROM RAT SENSORY NEURONS BYACTIVATING THE ADENOSINE 3',5'-CYCLIC-MONOPHOSPHATE TRANSDUCTION CASCADE

Prostaglandins sensitize sensory neurons to activation by mechanical, thermal and chemical stimuli, This sensitization also results in an in crease in the stimulus-evoked release of the neuroactive peptides, sub stance P and calcitonin gene-related peptide from sensory neurons, The cellular transduction cascade underlying the prostaglandin-induced au gmentation of peptide release is not known, Therefore, we examined whe ther the sensitizing action of prostaglandins on peptide release from sensory neurons grown in culture is mediated by the second messenger, adenosine 3', 5' cyclic monophosphate (cAMP), Prostaglandin E(2) and c arba prostacyclin (a stable analog of prostaglandin I-2) significantly increase the content of cAMP-like immunoreactive substance (icAMP) in the sensory neuron cultures at concentrations that also augment the b radykinin- or capsaicin-evoked release of peptides, Furthermore, pretr eating sensory neurons with agents that increase intracellular cAMP mi mics the sensitizing action of prostaglandins, Exposing cultures to ei ther forskolin (0.1-10 mu M), cholera toxin (1.5 mu g), or 8-bromo-cAM P (100 mu M) results in a significant enhancement of the bradykinin- o r capsaicin-stimulated release of both substance P-like and calcitonin gene-related peptide-like immunoreactive substances, Pretreating sens ory neurons with the adenylyl cyclase inhibitor, 9-tetrahydro-2-furyl adenine (5 mM), abolishes the prostaglandin-induced increases in icAMP content and attenuates the prostaglandin E, or carba prostacyclin enh ancement of the evoked release of calcitonin gene-related peptide-like immunoreactive substance, These results demonstrate that the cAMP tra nsduction cascade mediates the sensitizing actions of prostaglandins o n peptide release from sensory neurons.