Opioid inhibition of cholinergic transmission in the guinea-pig ileum is independent of intracellular cyclic AMP

This study examined whether the inhibitory actions of opioids in the guinea-pig ileum were influenced by agents which mimic or elevate intracellular cyclic adenosine 3′,5′-monophospate (cyclic AMP) levels. In longitudinal muscle-myenteric plexus preparations, the mu agonist, D-Ala², NMePhe⁴,Gly-ol⁵]enkephalin (DAGO) and the kappa agonist, dynorphin A-(1–13) depressed contractions of the longitudinal muscle evoked by electrical stimulation of myenteric neurons. Mean IC₅₀ values were 19 and 2.8 nM for DAGO and dynorphin, respectively. Neither forskolin, cholera toxin nor dibutyryl cyclic AMP affected significantlythe IC₅₀s for the opioid agonists. The experiments suggest that μ and agonists inhibit excitatory cholinergic transmission to the longitudinal muscle by intracellular effector mechanisms that do not involve cyclic AMP.