Norepinephrine-stimulated vascular prostacyclin synthesis. Receptor-dependent calcium channels control prostaglandin synthesis.
Norepinephrine-stimulated prostacyclin synthesis was studied in rat aortic rings by measuring 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by radioimmunoassay. Norepinephrine (10(-6) M) results in a 10- to 20-fold increase in 6-keto-PGF1 alpha synthesis by rat aortic rings (54 +/- 11 to 437 +/- 260 pg X mg wet weight-1 X 20 min-1). The maximal stimulation of 6-keto-PGF1 alpha synthesis was observed with a norepinephrine concentration of 10(-5) M at a mean effective concentration (EC50) of 9.5 +/- 3.2 X 10(-7) M which is similar to the contractile response (Emax = 10(-5) M, EC50 = 6.5 +/- 1.8 X 10(-7) M). Potassium chloride (30 mM), although causing a similar maximal contractile response as 10(-6) M norepinephrine, did not increase 6-keto-PGF1 alpha synthesis. Norepinephrine-stimulated 6-keto-PGF1 alpha synthesis was dependent upon extracellular calcium. Norepinephrine stimulation in Ca2+-free medium did not lead to a significant increase in 6-keto-PGF1 alpha synthesis. However, on the introduction of Ca2+, 6-keto-PGF1 alpha synthesis was restored to its initial level. Phentolamine (10(-6) M) (an alpha-adrenergic antagonist) and trifluroperazine (2.5 X 10(-4) M) (a calmodulin inhibitor) completely inhibited norepinephrine-stimulated 6-keto-PGF1 alpha synthesis, whereas verapamil 3 X 10(-6) M (a calcium channel blocking drug) only partially inhibited synthesis (control, 74 +/- 12; norepinephrine, 437 +/- 260; norepinephrine + verapamil, 123 +/- 8 pg X mg wet weight-1 X 20 min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D011453:Prostaglandins; D014268:Trifluoperazine; D015121:6-Ketoprostaglandin F1 alpha; D014700:Verapamil; D011464:Epoprostenol; D011188:Potassium; D009638:Norepinephrine; D010646:Phentolamine