Studies using animals genetically engineered to lack FP and examining the actions of EP4 receptor agonists in animals as well as animal and human tissues indicate that this receptor serves various functions. It has been regarded as the most successful therapeutic target among the 9 prostanoid receptors. Three FP receptor agonists are approved for clinical use in the USA viz.,
travoprost,
latanoprost, and
bimatoprost, and two additional agonists are prescribed in Europe and Asia viz.,
unoprostone and
tafluprost.
Hair growth Since FP receptors are expresses in human
dermal papillae and the use of FP agonists to treat glaucoma has as a side-effect an increase in eyelash growth, it has been suggested that FP agonists may be useful for treating baldness. This is supported by studies in the stump-tailed
Macaque primate model of androgen-induced scalp
alopecia which have found that the FP agonist,
latanoprost, promotes scalp hair growth. These studies have not yet been translated into baldness therapy in humans. FP
gene knockout in female mice blocks
parturition. That is, these FP-/- mice fail to enter labor even if induced by
oxytocin due to a failure in copus luteum regression and consequential failure to stop secreting
progesterone (declining progesterone levels trigger labor). Studies with monkey and human tissues allow that FP receptors may have a similar function in humans.
Bone PGF2α triggers the
NFATC2 pathway stimulating skeletal muscle cell growth. PGF2α, shown or presumed to operate by activating FP receptors, has complex effects on bone
osteoclasts and
osteoblasts to regulate
bone remodeling. However, further studies on the impact of the PGF2α-FP axis on bone are needed to better understand the pathophysiology underlying bone turnover and to identify this axis as a novel pharmacological target for the treatment of bone disorders and diseases.
Inflammation and allergy Unlike other prostaglandin receptors which have been shown in numerous studies to contribute to inflammatory and allergic responses in animal models, there are few studies on the function of FP receptors in these responses. Gene knockout studies in mice clearly show that FP mediates the late phase (
thromboxane receptor mediates the early phase) of the
tachycardia response to the pro-inflammatory agent,
lipopolysaccharide.
PTGFR knockout mice also show a reduction in the development of pulmonary fibrosis normally caused by microbial invasion or
bleomycin treatment. Finally, administration of PGF2α to mice causes an acute inflammatory response and elevated biosynthesis of PGF2α has been found in the tissues of patients with
rheumatoid arthritis,
psoriatic arthritis, and other forms of arthritis. While much further work is needed, these studies indicate that PGF2α-FP axis has some pro-inflammatory and anti-inflammatory effects in animals that may translate to humans.
Cardiovascular system PGF2α simulates an increase in
systolic blood pressure in
wild type but not FP(−/−) mice. Furthermore, FP(-/-) mice have significantly lower blood pressure, lower plasma
renin levels, and lower plasma
angiotensin-1 levels than wild-type mice, and FP agonists have a negative
inotropic effect to weaken the strength of heart beating in rats. Finally, FP(−/−) mice deficient in the
LDL receptor exhibit significantly less atherosclerosis than FP(+/+) LDL receptor-deficient mice. Activation of FP thus has pathophysiological consequences for the cardiovascular system relative to blood pressure, cardiac function, and atherosclerosis in animal models. The mechanism behind these FP effects and their relevancy to humans have not been elucidated. == Clinical significance ==