Evidence that 5-hydroxytryptamine may exert both facilitatory and inhibitory control of electrical field stimulation-evoked contractions in longitudinal muscle taken from the body of guinea-pig stomach.
Electrical field stimulation (FS) of guinea-pig stomach body longitudinal muscle strips caused frequency-related contractions mediated via cholinergic mechanisms. Metoclopramide (10(-8)-10(-5) M), MDL 72222 (10(-9)-10(-7) M) and 5-hydroxytryptophan (5-HTP) (3 X 10(-7)-2.4 X 10(-4) M) enhanced these contractions in all tissues, whereas 5-hydroxytryptamine (5-HT) (3 X 10(-8)-3 X 10(-5) M) enhanced the contractions, but only in approximately 15% of the tissues tested. FS-induced contractions were also enhanced in tissues treated in-vitro with p-chlorophenylalanine (2.5 X 10(-7)-2.5 X 10(-5) M) or monofluoromethyldopa (6 X 10(-7)-10(-4) M) or in tissues taken from animals having received p-chlorophenylalanine or monofluoromethyldopa. It is concluded that cholinergic-mediated contractions of stomach strips are subject to 5-HT modulation in two ways. The predominant action of endogenous 5-HT is to exert an inhibitory tone mediated via a metoclopramide and MDL 72222-sensitive 5-HT neuronal receptor. Exogenously applied 5-HT has little overt action to increase the essentially maximal inhibitory action of endogenous 5-HT, but acts on a 5-HT facilitatory receptor system to enhance contractions. Therefore, the actions of 5-HT agonists and antagonists to modify contractions in stomach strips will reflect the balance between 5-HT inhibitory and facilitatory influences, and the specificity of action of the compounds for the two 5-HT receptor systems.
Gunning
S J
SJ
Bradbury
A J
AJ
Costall
B
B
Naylor
R J
RJ
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D010134:Fenclonine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives / Q000494:pharmacology; D008787:Metoclopramide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects; D014326:Tropanes / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D012701:Serotonin; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D006916:5-Hydroxytryptophan; D008787:Metoclopramide; C042253:bemesetron; D010134:Fenclonine