Vascular actions of epidermal growth factor-urogastrone: possible relationship to prostaglandin production.
Epidermal growth factor-urogastrone (EGF-URO), a polypeptide of about 6000 atomic mass units present in humans, mice, rats, and other mammals that is widely recognized for its mitogenic and acid-inhibitory activities, was observed to cause contraction of helical arterial strips of the rat ileocolic artery and to potentiate the action of KCl on helical strips from the superior (cephalic) mesenteric artery. The contractile effect of EGF-URO in ileocolic preparations displayed marked tachyphylaxis at high EGF-URO concentrations (100 ng/mL). The apparent mean effective concentration for EGF-URO in these tissues was about 10 ng/mL (1.7 nM); the detection of EGF-URO degradation in the organ bath indicated that a half-maximal response may have been achieved at a concentration as low as 50% of this value (i.e., about 0.9 nM). The actions of EGF-URO were abolished by indomethacin (3 microM) and were, in part, mimicked by prostaglandin F2 alpha (PGF2 alpha), which contracted the ileocolic preparation and potentiated the action of KCl in the superior mesenteric preparation. In the superior mesenteric preparation, PGF2 alpha alone, like EGF-URO, did not have an appreciable effect on resting tension. The time lag of the EGF-URO effect in the ileocolic preparation (5-6 min to reach peak contraction) corresponded closely with the time course of EGF-URO-stimulated calcium accumulation measured previously in other cell systems. Our results suggest that EGF-URO acts to modulate contractility in vascular tissue via a cyclooxygenase pathway product (possibly PGF2 alpha). Our data point to a role for EGF-URO and possibly other growth factors in the control of vascular function.
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D015237:Dinoprost; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D011460:Prostaglandins F / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D011453:Prostaglandins; D011460:Prostaglandins F; D012701:Serotonin; D004815:Epidermal Growth Factor; D011189:Potassium Chloride; D015237:Dinoprost; D000527:Alprostadil; D009638:Norepinephrine; D007213:Indomethacin