9 alpha,11 beta-prostaglandin F2, a novel metabolite of prostaglandin D2 is a potent contractile agonist of human and guinea pig airways.
Prostaglandin (PG) D2, the predominant prostanoid released from activated mast cells in humans is initially metabolized by reduction of the C-11 keto function to yield 9 alpha,11 beta-PGF2. In this study the airways effects of 9 alpha,11 beta-PGF2 were compared with those of its epimer 9 alpha,11 alpha-PGF2 (PGF2 alpha) and PGD2. 9 alpha,11 beta-PGF2 was a potent contractile agonist of isolated guinea pig trachea and 4-mm human airways in vitro; the potencies of the PGs relative to PGD2 (= 1.00) being 0.65 (NS) and 4.08 (P less than 0.001) for 9 alpha,11 beta-PGF2, and 0.52 (P less than 0.01) and 2.40 (P less than 0.001) for PGF2 alpha, respectively. When inhaled by asthmatic subjects, 9 alpha,11 beta-PGF2 was a potent bronchoconstrictor agent, being approximately equipotent with PGD2 and 28-32 times more potent than histamine (P less than 0.01). These studies suggest that 9 alpha,11 beta-PGF2 is at least equipotent with PGD2 as a bronchoconstrictor agonist, and in being a major metabolite of PGD2, could contribute to the bronchoconstrictor effect of this mast cell-derived mediator in asthma.
Beasley
C R
CR
Robinson
C
C
Featherstone
R L
RL
Varley
J G
JG
Hardy
C C
CC
Church
M K
MK
Holgate
S T
ST
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D015237:Dinoprost; D005541:Forced Expiratory Volume; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D011457:Prostaglandins D; D011460:Prostaglandins F; D006632:Histamine; D015237:Dinoprost; D015230:Prostaglandin D2