Substance P and opioid interaction on stimulated and non-stimulated guinea pig ileum

In the past, substance P (SP) has been suggested to be both an opiate agonist and an antagonist. It therfore seemed appropriate to examine potential interactions of SP and opioids on guinea pig ileum. On non-stimulated ileal strips SP caused a dose responsive increase in contraction. Pretreatment of the tissue with morphine (3, 30, 300, 3000 nM), enkephalin (1.42, 14.2, 142, 1420 nM), naloxone (5nM), or atropine (0.144 micron) did not significantly alter the spasmogenic effect of SP. On stimulated guinea pig ileum, whereas morphine and enkephalin inhibited the electrically induced twitch, SP adminstration resulted in contraction of the tissue. Additionally, neither strongly effective non sub-threshold doses of SP antagonized the effects of the narcotics. These data are discussed in terms of separate receptors mediating the effects of the opiates and SP on guinea pig ileum.