Pre- and postjunctional effects of some prostanoids in human isolated vas deferens.
The effects of prostaglandin (PG) E1, PGE2, the thromboxane A2 analogue U-44069, and the prostacyclin derivative iloprost were studied on isometric contractions induced by norepinephrine (NE) and by electrical field stimulation of nerves in isolated preparations of the human vas deferens. The effects of these agents on the electrically induced release of 3H from preparations preincubated with [3H]NE were also investigated. PGE1 and PGE2 inhibited the electrically induced contractions concentration dependently. U-44069 augmented the contractions without affecting baseline tension, and in preparations where the contractions had been inhibited by PGE1 or PGE2, U-44069 restored the contractions almost to starting levels. The thromboxane A2-receptor antagonist BM 13505, having no effect or inhibitory effects on electrically induced contractions, abolished the stimulatory effect of U-44069. Contractions induced by exogenous NE were augmented by U-44069, whereas PGE1 and BM 13505 were without effects. The electrically induced release of 3H was inhibited by PGE1 and PGE2 in a concentration-dependent manner, whereas U-44069 and BM 13505 increased the release of 3H. Furthermore, the inhibitory effect of PGE1 on 3H release was partly counteracted by U-44069. Iloprost had no significant effect on electrically induced contractions or on 3H release. These results suggest that, in the human vas deferens, thromboxane A2 augments contractions predominantly through a postjunctional site of action, whereas PGs of the E type have a prejunctional inhibitory effect. In addition, the pre- and post-junctional effect profiles of U-44069 and BM 13505 suggest that there may be more than one thromboxane receptor.
Holmquist
F
F
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Hedlund
H
H
Andersson
K E
KE
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004558:Electric Stimulation; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000502:physiology; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology*
D010648:Phenylacetates; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; C028429:U 44069; D013928:Thromboxane A2; D000527:Alprostadil; D016285:Iloprost; D015232:Dinoprostone; C051762:daltroban; D009638:Norepinephrine