Characterization of the prostanoid receptors and of the contractile effects of prostaglandin F2ain human pial arteries

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Abstract
The contractile and relaxant effects of various prostanoids were studied on isolated human pial arteries. Contractions were elicited with the following order of potency: U46619 [(15S)-hydroxy-11.alpha.,9.alpha.-(epoxymethano)prosta-5Z,13E-dienoic acid] .apprxeq. [(15S)-hydro-9.alpha.,11.alpha.-(epoxymethano)prosta-5Z,13E-dienoic acid] U44069 > PGB2 [prostaglandin B2] > PGF2.alpha. > PGE2 .apprxeq. PGD2 .apprxeq. PGF1.alpha. .gtoreq. TXB2 [thromboxane B2] indicating that prostanoid-induced contractions probably are mediated by a thromboxane-sensitive receptor. Relaxation of PGF2.alpha.-contracted arteries was induced with the order of potency: PGE2 > PGE1 > PGD2 .apprxeq. PGD1. Vessels contracted by K+ were relaxed only by PGE1. Since PGI2 was more potent than all the prostanoids tested in this study, relaxant responses are probably mediated via a PGI2-sensitive receptor. The roles of free extracellular and cellularly bound Ca for the contractile effects of PGF2.alpha. and K+ were estimated by incubating the arteries for various times in Ca-free medium containing 10-5 M EGTA [ethylene glycol bis (.beta.-amino ethyl ether) N,N,N'',N''-tetraacetic acid]. Incubation for 5-10 min abolished K+-induced contractions, whereas after 40 min of incubation PGF2.alpha.-induced contractions that reached 70% of control. The PGF2.alpha.-induced contraction was biphasic in 8 of 10 preparations. The 2nd phase could be eliminated by increasing the EGTA-concentration to 104 M, as well as by nifedipine pretreatment. In Ca-free, high K+ medium C-induced contractions were elicited at lower concentrations in the presence of PGF2.alpha.. Evidently, PGF2.alpha.-induced contractions in human pial arteries are relatively independent of free extracellular Ca. PGF2.alpha. may promote trans-membrane influx of Ca, as well as release Ca from seemingly superficially located cellular stores.