1. Replacement of the carboxylic acid group of PGF(2α) with the non-acidic substituents hydroxyl (-OH) or methoxy (-OCH3) resulted in an unexpected activity profile. 2. Although PGF(2α) 1-OH and PGF(2α) 1-OCH3 exhibited potent contractile effects similar to 17-phenyl PGF(2α) in the cat lung parenchymal preparation, they were approximately 1000 times less potent than 17-phenyl PGF(2α) in stimulating recombinant feline and human FP receptors. 3. In human dermal fibroblasts and Swiss 3T3 cells PGF(2α) 1-OH and PGF(2α) 1-OCH3 produced no Ca2+ signal until a 1 μM concentration was exceeded. Pretreatment of Swiss 3T3 cells with either 1 μM PGF(2α) 1-OH or PGF(2α) 1-OCH3 did not attenuate Ca2+ signal responses produced by PGF(2α) or fluprostenol. In the rat uterus, PGF(2α) 1-OH was about two orders of magnitude less potent than 17-phenyl PGF(2α) whereas PGF(2α) 1-OCH3 produced only a minimal effect. 4. Radioligand binding studies on cat lung parenchymal plasma membrane preparations suggested that the cat lung parenchyma does not contain a homogeneous population of receptors that equally respond to PGF2(α)1-OH, PGF(2α)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(2α) 1-OH and PGF(2α) 1-OCH3 could not be ascribed to interaction with these receptors. 6. The potent effects of PGF(2α) 1-OH and PGF(2α) 1-OCH3 on the cat lung parenchyma are difficult to describe in terms of interaction with the FP or any other known prostanoid receptor.
- FP receptor
- Prostaglandin F(2α) (PGF(2α))
- Radioligad binding
ASJC Scopus subject areas