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University of California

Des-tyr Dynorphin Partnership

Nancy M Lee

Horace H Loh

Jaw-Kang Chang

Peter Wung Lee

Edward Tak Wei

Akira E Takemori

Yoshio Hosobuchi

The disclosure provides methods and compositions useful for identifying a subject's predisposition to a gastrointestinal disease or disorder.

Method to predict or diagnose a gastrointestinal disorder or disease

Method to predict or diagnose a gastointestinal disorder or disease

Novel peptides of the invention are dynorphin analogues and have similar activity to endogenous dynorphin, but are des-Tyr or des-Tyr-Gly with respect to endogenous dynorphin and have at least seven amino acid residues. The novel peptides have therapeutic uses, such as administration to a host tolerant to a narcotic analgesic in order to potentiate activity of the narcotic analgesic and/or to block withdrawal symptoms.

Des-Tyr dynorphin analogues

A method of treatment for patients suffering from cerebral ischemia is provided by administering an opioid peptide. Particulary preferred is the administration of dynorphin, or dynorphin-related peptides, in the acid or amidated form. Practice of the invention is useful in prolonging survival.

Method of treating cerebral ischemia

A method is provided for treating high blood pressure and disturbances of cardiac function by administering a therapeutically effective dosage of dynorphin-related opioid peptides, such as dynorphin(1-13) and dynorphin(1-10) amide, having at least ten amino acids linked sequentially by peptide bonds and with the five amino acids from the N-terminal end being the same as, or mimicking, Leu-enkephalin. Administration may be over a period of time, as for individuals with chronic high blood pressure, and may be by dispensing the medicament in aerosol form.

Method for controlling blood pressure

Dynorphin(1-13) has been previously reported to antagonize the analgesia induced by narcotics in naive hosts. Novel compounds are provided which differ from dynorphin(1-13) by neither potentiating nor antagonizing narcotics, such as morphine, in naive animals. In tolerant hosts the new compounds potentiate narcotic or peptide induced analgesia, and in addition are less susceptible to degradation than dynorphin(1-13). Particularly preferred of the new compounds are polypeptides having ten amino acids with nitrogen containing moieties at both termini.

Dynorphin amide analogs

A therapeutic method of using dynorphin comprises administering dynorphin to a host tolerant to narcotic analgesics. Practice of the therapeutic method provides that lower doses of a narcotic analgesic may be used, such as for patients requiring chronic treatment with narcotics to ease pain, and for treatment of narcotics addicts.

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San Francisco, CA, United States of America

Nancy M Lee