Characterization of the inhibitory 5-HT receptor in the rat vas deferens.
The inhibitory effects of 5-HT on the response of the rat isolated rat vas deferens preparation to electrical stimulation (0.1 Hz) has been investigated. A number of compounds, previously shown to possess antagonist activity at the rat central nervous system 5-HT autoreceptor, including methiothepin and the beta-blockers propranolol, alprenolol and cyanopindolol, have been found to possess virtually identical activity in the rat vas deferens. Cyanopindolol (Ke versus 5-HT = 4.9 nM) was the most potent antagonist tested, but was even more effective as a beta 2-antagonist (Ke = 0.14 nM) in this preparation. Prizidilol (Ke versus 5-HT = 30.2 nM, Ke versus isoprenaline = 75 nM) and acebutolol (Ke versus 5-HT = 297 nM, Ke versus isoprenaline = 3300 nM) have been identified as beta-blocking compounds that possess higher activity at the 5-HT receptor than at the beta 2-receptor. Several compounds, previously shown to possess 5-HT agonist activity, have been tested in this preparation and their potencies relative to 5-HT were as follows: 5-carboxyamidotryptamine (x 7), TFMPP (x 0.1) and LSD (x 0.04). RU24969 was found to behave as a low intrinsic activity partial agonist. All the evidence is consistent with the inhibitory 5-HT receptor present in this preparation being identical to the 5-HT autoreceptor found in the rat central nervous system which has been identified as the receptor with which the 5-HT1B binding site is associated.
Smith
C F
CF
Reckitt and Colman Pharmaceuticals, Humberside, England.
Bennett
R T
RT
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D008784:Methysergide