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Dissertation
Peripheral mechanisms related to the anorectic action of serotonergic stimulation
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania
1992
DOI:
https://doi.org/10.17918/00008615
Abstract
These studies describe mechanisms by which peripheral serotonin (5-HT) reduces food intake in rats. Experiments compared mechanisms recruited by 5-HT to those of a model satiety system mediated by cholecystokinin (CCK). Initial studies examined whether stimulation of CCK-A receptors was required for anorexia following systemic 5-HT. Pretreatment of animals with the CCK-A receptor antagonist, devazepide, blocked CCK-stimulated anorexia but did not alter 5-HT-induced reductions in food intake. These studies demonstrated that mechanisms recruited by 5-HT, unlike CCK, were independent of CCK-A receptor stimulation. Additional studies examined whether an intact abdominal vagus nerve was required to elicit anorexia following peripherally-administered 5-HT. After vagotomy, CCK-mediated anorexia was blocked, but in the same animals, the effect of 5-HT on food intake was unaltered. Thus, unlike, CCK, peripheral 5-HT reduced food intake by vagally-independent mechanisms. The surgeries were verified immunohistochemically using anti-neurofilament protein to stain axons. Final studies considered the actions of 5-HT on the pylorus as one gastric site where 5-HT might act to alter feeding. These studies characterized the pharmacological profile for 5-HT-induced contraction of the pylorus in vitro. The complete response-curve for 5-HT-induced contraction of the pylorus was generated using a classical smooth muscle assay. Antagonist studies revealed that the 5-HT-stimulated contraction was blocked by diltiazem, ketanserin, xylamidine, and methysergide, but was insensitive to tetrodotoxin, ICS 205-930, prazosin, devazepide, and (-)pindolol pretreatment. Thus, it was inferred that a 5-HT2-type receptor, located on smooth muscle, mediated contraction to 5-HT in rat pylorus. The pharmacology of 5-HT-induced contraction of the pylorus agrees with in vivo studies demonstrating a peripheral 5-HT2 receptor mechanism mediating the anorectic action of peripheral 5-HT in rats. This correlation justifies further functional studies examining the pylorus as a site where peripheral 5-HT might alter feeding in rats. Overall, this thesis defines peripheral mechanisms for 5-HT control of feeding by dissociating its actions from those of CCK, providing the basis for future investigations of the sites of action of peripheral 5-HT in controlling ingestive behavior.
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Details
- Title
- Peripheral mechanisms related to the anorectic action of serotonergic stimulation
- Creators
- Kim Eberle-Wang
- Awarding Institution
- Medical College of Pennsylvania
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania; Philadelphia, Pennsylvania
- Number of pages
- xi, 181 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Medical College of Pennsylvania (1970-1993)
- Other Identifier
- 991021888914704721