The proenkephalin A fragment metorphamide shows supraspinal and spinal opioid activity in vivo.
Metorphamide (Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2) a novel amidated octapeptide fragment of proenkephalin A was synthesized, purified and subsequently shown to inhibit the reflex contractions of the rat urinary bladder following intracerebroventricular and spinal intrathecal microinjections. The effects of metorphamide were consistently antagonized by naloxone but not by the delta-opioid receptor antagonist ICI 174,864. Comparison of metorphamide with other proenkephalin A fragments suggested that the activity of this peptide was not due to in vivo processing to other active fragments. These data suggest that metorphamide has potent in vivo mu-opioid activity but little delta-opioid receptor activity.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology
D000596:Amino Acids; D004744:Enkephalin, Methionine; C039700:adrenorphin