Multiple mu receptors: evidence for mu2 sites in the guinea pig ileum

The ability of morphine to inhibit the electrically induced contractions of the guinea pig ileum is mediated through the mu class of opioid receptors. However, recent studies have implied the existence of two subtypes of mu receptors in the brain (mu1 and mu2), which differ both biochemically and pharmacologically. The antagonist naloxonazine and the agonist oxymorphonazine selectively and irreversibly bind mu1 sites. Treatment of both rat and guinea pig brain homogenates with naloxonazine in vitro to selectively inhibit mu1 binding significantly decreased [3H]dihydromorphine binding, whereas binding in similarly treated guinea pig ileum longitudinal muscle-myenteric plexus was virtually unaffected (P less than 0.0005). Similarly, the actions of both drugs in the guinea pig ileum contraction assay were reversible. The findings imply that morphine's actions on the guinea pig ileum were mediated through the mu2 subtype of opioid receptor.