5-Hydroxytryptamine affects rat migrating myoelectric complexes through different receptor subtypes: evidence from 5-hydroxytryptophan administration.
The effect of the serotonin precursor 5-hydroxytryptophan (5-HTP) on jejunal migrating myoelectric complexes (MMCs) was investigated in conscious rats. Subcutaneous administration of low doses of 5-HTP (1-2 mg/kg) shortened the period between migrating complexes, whereas high doses of the compound (4-8 mg/kg) disrupted the MMC pattern. The serotonin (5-HT2) antagonist methysergide (8 mg/kg s.c.) did not alter basal MMC, neither did it prevent the effect of a low dose of 5-HTP; conversely, it antagonized the disruption due to the high dose. The 5-HT3 antagonist ICS 205-930 (30 micrograms/kg s.c.) decreased MMC frequency; administration of 2 mg/kg 5-HTP following ICS 205-930 brought the frequency of myoelectric complexes back to basal values. Both effects of 5-HTP were prevented by the decarboxylase inhibitor benserazide (85 mg/kg i.p.), which per se caused a transient inhibition of spiking activity. The results suggest that rat MMCs can be influenced in a composite fashion by progressively increasing concentrations of 5-HT, which in turn activate different receptor subtypes. A peripheral neuronal receptor, probably belonging to the 5-HT3 subclass, mediates the increase in MMC frequency observed after low doses of 5-HTP; higher levels of serotonin activate 5-HT2 receptors, causing disruption of cycling activity. Additionally, 5-HT3 receptors, but not 5-HT2, appear to be relevant for the regulation of the MMC pattern by the endogenous amine.
Sagrada
A
A
Department of Pharmacology, Istituto De Angeli, Milan, Italy.
Brancaccio
N
N
Schiavone
A
A
D006916:5-Hydroxytryptophan; D000818:Animals; D001545:Benserazide; D004569:Electroencephalography; D007211:Indoles; D007583:Jejunum / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D008784:Methysergide; D009132:Muscles / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D000077526:Tropisetron
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000077526:Tropisetron; D001545:Benserazide; D006916:5-Hydroxytryptophan; D008784:Methysergide