Characterization of the prostanoid receptors and of the contractile effects of prostaglandin F2 alpha in human pial arteries.
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 approximately equal to U44069 greater than PGB2 greater than PGF2 alpha greater than PGE2 approximately equal to PGD2 approximately equal to PGF1 alpha greater than or equal to TXB2, 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 greater than PGE1 greater than PGD2 approximately equal to PGD1. Vessels contrated by K+ were relaxed only by PGE1. Since PGI2 was previously found to be more potent than all the prostanoids tested in the present study, relaxant responses are probably mediated via a PGI2-sensitive receptor. The role of free extracellular and cellularly bound calcium for the contractile effects of PGF2 alpha and K+ were estimated by incubating the arteries for various times in calcium-free medium containing 10(-5) M EGTA. Incubation for 5-10 min abolished K+-induced contractions, whereas after 40 min of incubation PGF2 alpha still induced contractions that reached 70% of control. The PGF2 alpha-induced contraction was biphasic in 8 out of 10 preparations. The second phase could be eliminated by increasing the EGTA-concentration to 10(-4) M, as well as by nifedipine pretreatment. In calcium-free, high K+ medium calcium-induced contractions were elicited at lower concentrations in the presence of PGF2 alpha. The results suggest that PGF2 alpha-induced contractions in human pial arteries are relatively independent of free extracellular calcium. PGF2 alpha may promote trans-membrane influx of calcium, as well as release calcium from seemingly superficially located cellular stores.
D002118:Calcium / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011188:Potassium / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000502:physiology*; D013189:SRS-A / Q000037:antagonists & inhibitors
D011453:Prostaglandins; D011460:Prostaglandins F; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D013189:SRS-A; D004533:Egtazic Acid; D015237:Dinoprost; D009543:Nifedipine; D011188:Potassium; D002118:Calcium