Central and peripheral administration of serotonin produces opposite effects on mouse colonic propulsive motility.
The effects of central or peripheral administration of serotonin on colonic expulsion time (CE) of a glass bead were evaluated after i.p. or free hand i.c.v. administration to mice. Serotonin (5-HT) caused an inhibition of CE when administered centrally but stimulated propulsion after i.p. administration. Several selective serotonin agonists were then tested. Inhibition after i.c.v. administration was produced by 8-OH-DPAT (5-HT1a), RU-24969 (5-HT1b), and 2-methyl serotonin (5-HT3), but not DOI (5-HT2) which augmented propulsion. Relative potencies for inhibition (ED50S) were RU (0.9 micrograms, 3.9 nM) greater than 8-OH-DPAT (3 micrograms, 9.1 nM) greater than 5-HT (7.8 micrograms, 20.1 nM) greater than 2-methyl serotonin (43 micrograms, 140 nM). After i.p. administration 5-HT stimulated propulsive motility (ED50 = 16.1 micrograms, 41.4 nM) while 8-OH-DPAT (ED50 = 55 micrograms, 167 nM) and RU-24969 (ED50 = 54 micrograms, 236 nM) inhibited. DOI and 2-MS had no dose-related activity. The finding that several of the serotonin receptor agonists were capable of inhibiting propulsive motility either by i.p. or i.c.v. administration is a new finding and may help to explain drug-induced constipating activity in man. No selective agonist completely mimicked the effect of serotonin.
Jacoby
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HI
R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Bonfilio
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AC
Raffa
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RB
D000818:Animals; D003106:Colon / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology
D011985:Receptors, Serotonin; D012701:Serotonin