μ and δ receptors belong to a family of receptors that are coupled to potassium channels

The effects of agonists at μ and δ opioid receptors were compared by measuring membrane currents under voltage clamp from neurons of the rat nucleus locus coeruleus and guinea pig submucous plexus. In each tissue, the appropriate selective agonist (Tyr-D-Ala-Gly-MePhe-Gly-ol for μ receptors in locus coeruleus or Tyr-D-Pen-Gly-Phe-D-Pen for δ receptors in submucous plexus) increased the conductance of an inwardly rectifying potassium conductance and strongly hyperpolarized the membrane. The properties of the potassium conductance affected by the two opioids could not be distinguished. Experiments with intracellular application of guanosine 5'-[γ-thio]triphosphate indicated that a guanine nucleotide-binding regulatory protein was involved in the coupling between opioid receptor and potassium channel, but there was no evidence for activation of either cAMP-dependent protein kinase or protein kinase C. It is noted that a number of vertebrate neurotransmitter receptors are coupled to potassium channels. The potassium conductance associated with these channels has properties similar to the conductance activated by μ and δ opioids; this family includes the following receptors: acetylcholine M₂, norpinephrine α₂, dopamine D₂, 5-hydroxytryptamine 5-HT₁, adenosine A₁, γ-aminobutyric acid GABA(B), and somatostatin. It is suggested that this conductance is a conserved neuronal effector coupled to one of the receptor types that mediates the effects of each of several major transmitters. The μ and δ opioid receptors appear to be unusual in that both utilize this same effector mechanism.