Characterization of contraction-mediating prostanoid receptors in human penile erectile tissues.
The effects of the thromboxane-receptor antagonist L-636,499 were studied on contractions induced by the thromboxane A2 mimic U44069 and by prostaglandin F2 alpha in isolated preparations of the human corpus cavernosum and corpus spongiosum. The objectives were to characterize prostanoid receptors and, in particular, to elucidate whether more than one receptor was involved in prostanoid-induced contraction of penile erectile tissues. L-636,499 at concentrations 10(-6) M to 3 x 10(-5) M induced a parallel shift to the right of the concentration-response curve to U44069 in both corpus cavernosum and corpus spongiosum suggesting competitive antagonism. Schild plots using U44069 as the agonist and L-636,499 as the antagonist revealed slope indexes near unity in both tissues, and the pA2 values were almost identical. In contrast, L-636,499 concentration-dependently reduced the maximum response to prostaglandin F2 alpha, indicating a non-competitive action. The results suggest that the main contraction-mediating prostanoid receptor in human penile erectile tissues is a thromboxane A2 sensitive receptor. However, the presence of more than one contraction-mediating prostanoid receptor cannot be excluded.
Hedlund
H
H
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Andersson
K E
KE
Fovaeus
M
M
Holmquist
F
F
Uski
T
T
D000328:Adult; D000368:Aged; D003988:Dibenzothiepins / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010410:Penile Erection; D010413:Penis / Q000294:innervation*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000302:isolation & purification*; D017482:Receptors, Thromboxane
D003988:Dibenzothiepins; D011448:Prostaglandin Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C028429:U 44069; C047685:L 636499; D015237:Dinoprost