Oral bronchodilator effect of 16(S)-methyl-20-methoxy-PGE2 (YPG-209) in guinea-pigs.

The bronchodilator activity of synthetic 16(S)-methyl-20-methoxy-PGE2 (YPG-209) was investigated in guinea-pigs. The potency of YPG-209 in relaxing the isolated trachea contracted by histamine was 10 times smaller than that of PGE2, and was not reduced by propranolol, while in the anesthetized animals YPG-209 given by an intravenous route was 230 times as potent in inhibiting an increase in the airway resistance induced by histamine as PGE2. When administered either intraduodenally to the anesthetized animals or orally to the conscious ones, YPG-209 showed a pronounced protection against histamine-induced bronchoconstriction, in contrast to PGE2 which had no significant protecting effect. Neither hypotension nor diarrhea could be observed at the doses of YPG-209 exhibiting a considerable bronchodilator effect. The hydroxyl group at carbon-15 of YPG-209 was little oxidized by 15-hydroxy prostaglandin dehydrogenase which was purified from the lung of guinea-pigs, consistent with the comparably long lasting bronchodilator activity of YPG-209 in vivo.