The mode of action of prostaglandin E2, F2 alpha and prostacyclin on vesicourethral smooth muscle.
Interactions of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha) and prostacyclin (PGI2) with Ca2+ on the isometric contraction of rabbit detrusor muscle strips were studied using two types of Ca2+ antagonists of different mechanisms of action: verapamil and sodium nitroprusside (NP). The effects of PGI2 on vesicourethral smooth muscle and their relationship with cholinergic, adrenergic receptors and nervous activity were also investigated. PGE2 and F2 alpha (3 X 10(-8) to 3 X 10(-5) M) caused dose-dependent contraction of the strips. Pretreatment of the strips with verapamil (10(-7) to 10(-5)M) significantly inhibited PGs-induced contraction in a dose-dependent manner, whereas NP(10(-7) to 10(-5)M) failed to suppress the contraction. Relaxation of the preparations once contracted by PGE2 and F2 alpha (3 X 10(-6)M) was induced completely by addition of verapamil (10(-5)M), and incompletely by NP(10(-5) to 10(-3)M). Washing of the strips with Ca2+-free solution containing 0.01 mM EGTA completely eliminated spontaneous activity and diminished basal tension, but replenishment of Ca2+ (0.5 to 10 mM) to the medium caused dose-related contraction and spontaneous activity of the strips. Addition of PGE2 and F2 alpha to the Ca2+-free medium enhanced Ca2+-induced contraction and spontaneous activity during Ca2+ replenishment, which were significantly inhibited by pretreatment with verapamil (10(-7) to 10(-5)M) in a dose-dependent manner, but not affected by NP (10(-7) to 10(-5)M). In Ca2+-free medium containing 0.1 mM EGTA, PGE2 and F2 alpha caused a slight degree of tension increase of the strips dose-dependently at the higher concentration exceeding 3 X 10(-6)M. PGI2 (10(-9) to 3 X 10(-4)M) caused dose-dependent contraction of the strips from the bladder body, base and the urethra. The contractile action of PGI2 was greatest on the bladder body, less on the base and minimal on the urethra. The effect of PGI2 was less potent than those of PGE2 and F2 alpha. The PGI2-induced contraction was slow in onset, short lasting, and not affected by pretreatment with phentolamine, propranolol, atropine, hexamethonium, hemicholinium-3 and tetrodotoxin. The interactions of PGI2 with Ca2+ were similar to those of PGE2 and F2 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology*; D011817:Rabbits; D014521:Urethra / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D011458:Prostaglandins E; D011460:Prostaglandins F; D009599:Nitroprusside; D015237:Dinoprost; D014700:Verapamil; D011464:Epoprostenol; D015232:Dinoprostone; D002118:Calcium