Df. Woodward et al., Replacement of the carboxylic acid group of prostaglandin F2 alpha with a hydroxyl or methoxy substituent provides biologically unique compounds, BR J PHARM, 130(8), 2000, pp. 1933-1943
1 Replacement of the carboxylic acid group of PGF(2 alpha) with the non-aci
dic substituents hydroxyl (-OH) or methoxy (-OCH3) resulted in an unexpecte
d activity profile.
2 Although PGF(2 alpha) 1-OH and PGF(2 alpha) 1-OCH3 exhibited potent contr
actile effects similar to 17-phenyl PGF(2 alpha) in the cat lung parenchyma
l preparation, they were approximately 1000 times less potent than 17-pheny
l PGF(2 alpha) in stimulating recombinant feline and human FP receptors.
3 In human dermal fibroblasts and Swiss 3T3 cells PGF(2 alpha) 1-OH and PGF
(2 alpha) 1-OCH3 produced no Ca2+ signal until a 1 mu M concentration was e
xceeded. Pretreatment of Swiss 3T3 cells with either 1 mu M PGF(2 alpha) 1-
OH or PGF(2 alpha) 1-OCH3 did not attenuate Ca2+ signal responses produced
by PGF(2 alpha) or fluprostenol. In the rat uterus, PGF(2 alpha) 1-OH was a
bout two orders of magnitude less potent than 17-phenyl PGF(2 alpha) wherea
s PGF(2 alpha) 1-OCH3 produced only a minimal effect.
4 Radioligand binding studies on cat lung parenchymal plasma membrane prepa
rations suggested that the cat lung parenchyma does not contain a homogeneo
us population of receptors that equally respond to PGF(2 alpha) 1-OH, PGF(2
alpha) 1-OCH3, and classical FP receptor agonists.
5 Studies on smooth muscle preparations and cells containing DP, EP1, EP2,
EP3, EP4, IP, and TP receptors indicated that the activity of PGF(2 alpha)
1-OH and PGF(2 alpha) 1-OCH3 could not be ascribed to interaction with thes
e receptors.
6 The potent effects of PGF(2 alpha) 1-OH and PGF(2 alpha) 1-OCH3 on the ca
t lung parenchyma are difficult to describe in terms of interaction with th
e FP or any other known prostanoid receptor.