Contraction of guinea pig trachea by epidermal growth factor--urogastrone.
To evaluate further the action of epidermal growth factor - urogastrone (EGF-URO) in smooth muscle systems, we examined the effect of the peptide on guinea pig tracheal strips. The cumulative addition of EGF-URO to the organ bath resulted in a concentration-dependent tonic contraction without tachyphylaxis. The half-maximal contraction was obtained at 13 +/- 3 ng/mL EGF-URO (2 nM). The maximum contraction at 100 ng/mL approached 60% of that induced by 1 microM histamine. No significant difference in the EGF-URO-induced contraction was observed in the presence or absence of a functional epithelium. Preincubation with 1 microM indomethacin for 20 min abolished the action of EGF-URO. The contractile effect of EGF-URO was not affected by yohimbine, propranolol, atropine, tetrodotoxin, and esculetin. However, mepacrine caused inhibition by 37 +/- 7% (mean +/- SEM for n = 3). Verapamil (10 microM) inhibited the EGF-induced response by 62 +/- 5% (mean +/- SEM for n = 4); the response was also absent in Ca-free (1 mM EGTA) buffer. However, the response was restored after the readdition of calcium. Our results suggest that EGF-URO can modulate tracheal smooth muscle contractility via a cyclooxygenase product and raise the possibility that EGF-URO might play a role in controlling pulmonary smooth muscle tone in vivo.
Patel
P
P
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Alta., Canada.
Itoh
H
H
Lederis
K
K
Hollenberg
M D
MD
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D004533:Egtazic Acid; D004815:Epidermal Growth Factor; D002118:Calcium; D007213:Indomethacin