5-HT4 receptors in isolated human corpus cavernosum?
The novel serotonin subtype-4 (5-HT4) receptor agonist, SC53116 (SC), produced a limited relaxation of noradrenaline (NA) pre-contracted human corpus cavernosum (CC) smooth muscle in vitro. This effect was not significantly attenuated by the 5-HT4 antagonist SDZ250557 (SDZ). In the presence of (+/-) pindolol (1 microM) and methysergide (1 microM), employed to mask 5-HT1 and beta-adrenergic, and 5-HT2 receptors respectively, SC failed to relax NA pre-contracted CC strips to a greater extent than saline. Functional cAMP dependent relaxation pathways were demonstrated by a significant reduction in NA induced tone by prostaglandin E1 (PGE1) and isopropylnoradrenaline (IPNA), the action of the latter compound was effectively eliminated in the presence of (+/-) pindolol. Relaxation of NA induced tone caused by the nitric oxide donor nitro-glycerine (NTG) was significant and similar in the absence and presence of the 5-HT and beta-adrenergic antagonists. The results of this present study indicate that human corporal smooth muscle does not contain 5-HT4 receptors and that, although compounds like SC act to relax non-vascular smooth muscle via cAMP dependent mechanisms, 5-HT4 receptor agonists may be expected to be of limited utility in triggering cAMP dependent relaxation responses in human CC.
Hayes
E S
ES
Department of Obstetrics & Gynaecology, National University of Singapore.
Adaikan
P G
PG
Ratnam
S S
SS
Ng
S C
SC
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D006801:Humans; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010413:Penis / Q000502:physiology*; D010869:Pindolol / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D062366:para-Aminobenzoates
D000319:Adrenergic beta-Antagonists; D001549:Benzamides; D011758:Pyrroles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D062366:para-Aminobenzoates; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; C074211:SC 53116; D044422:Receptors, Serotonin, 5-HT4; D010869:Pindolol; D010129:4-Aminobenzoic Acid; D009638:Norepinephrine; D008784:Methysergide