Role of alpha 1-adrenoceptors and 5-HT2 receptors in serotonin-induced contraction of rat prostate: autoradiographical and functional studies.
Urinary obstruction from benign prostatic hyperplasia is a common clinical problem possibly associated with excessive prostatic constriction around the urethra. These studies compared adrenergic and serotonergic functional activity to specific alpha 1 and serotonin (5-hydroxytryptamine; 5-HT) binding sites in the rat prostate. Isolated, left ventral lobes of the rat prostate were removed and examined for in vitro contraction. Norepinephrine-induced contraction of the rat prostate was competitively blocked by prazosin with an apparent antagonist dissociation constant (pKB) of 8.13. 5-HT also contracted the rat prostate. However, in the presence of prazosin, maximum 5-HT contraction was reduced by half suggesting that high concentrations of 5-HT can activate alpha 1 receptors in the prostate. The concentration-response curve to 5-HT in the presence of 1 microM prazosin was competitively inhibited by the 5-HT2 receptor antagonist LY53857 (6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid 2-hydroxyl-1-methylpropylester (Z)-2-butenedioate (1:1)) (pKB = 9.02). Autoradiographic studies with [125I]LSD (2-iodo-lysergic acid diethylamide) documented the presence of 5-HT2 receptors since significant displacement of the radioligand occurred with 5-HT and LY53857, but not with prazosin. The alpha 1-adrenoceptor ligand [125I]HEAT ([beta-(4-hydroxy-3-iodophenyl)ethylaminomethyl]-tetralone) confirmed the presence of alpha 1-adrenoceptors in the rat prostate since significant displacement of the radioligand occurred with prazosin, but not 5-HT or LY53857. The inability of prazosin to displace [125I]LSD and the inability of 5-HT to displace [125I]HEAT suggest that 5-HT cannot directly interact with alpha 1-adrenoceptors in the prostate.(ABSTRACT TRUNCATED AT 250 WORDS)
Killam
A L
AL
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Watts
S W
SW
Cohen
M L
ML
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008238:Lysergic Acid Diethylamide; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010627:Phenethylamines; D011467:Prostate / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D044024:Tetralones
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007457:Iodine Radioisotopes; D010627:Phenethylamines; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D044024:Tetralones; D012701:Serotonin; C010652:BE 2254; D008238:Lysergic Acid Diethylamide; D009638:Norepinephrine