Photoactivation mechanism of hyaluronidase by chlorpromazine.
A pre-irradiated chlorpromazine (CPZ) in pH 7.2 and aqueous solutions activated hyaluronidase, and it showed the enzyme-activating action even after 7 days of irradiation. This indicates that the stable photoproducts of CPZ activated the enzyme. But promazine and CPZ-5-sulfoxide, which are photoproducts of CPZ, did not activate the enzyme in the presence and absence of UVA. The dimer and higher molecular weight (MW) products of CPZ that were obtained by treating the pre-irradiated CPZ solution with gel permeation chromatography showed the hyaluronidase by activating action without UVA. In addition, photoactivation of hyaluronidase by CPZ was inhibited by radical quenchers. This suggested that the photoproducts with enzyme-activating action were produced via some radicals. On the basis of these findings, a possible mechanism for photoactivation of hyaluronidase by CPZ was proposed.
Department of Pharmacy, Faculty of Pharmaceutical Science, Tokushima Bunri University, Japan.
H
H
Matsumoto
H
H
Kakegawa
N
N
Shigehara
H
H
Miyataka
N
N
Mitsuo
T
T
Satoh
T
T
Irie
K
K
Uekama
D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D002746:Chlorpromazine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D008027:Light; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D006821:Hyaluronoglucosaminidase; D002746:Chlorpromazine