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ICS 205-930 and feeding responses to amino acid imbalance: a peripheral effect?
B J Hrupka1, D W Gietzen, J L Beverly
1Department of Physiological Sciences, School of Veterinary Medicine University of California, Davis 95616.
Serotonin3 (5-HT3) receptor antagonists (ICS 205-930 and MDL 72222) have been shown to block or ameliorate the anorectic response of the rat to amino acid imbalanced (IMB) diets. Two experiments were conducted to determine whether the effects of these antagonists are mediated through central or peripheral 5-HT3 receptors. In Experiment One, ICS 205-930 (ICS) was injected centrally, into either the lateral ventricle (doses: 0.3 pmol to 10 nmol), or the cisterna magna (62 nmol). The intake of rats fed an isoleucine IMB diet was not affected by these injections. In Experiment Two, rats received an IP injection of either saline, ICS, or a quaternized derivative of ICS (Q-ICS) that should not cross the blood-brain barrier. Both ICS- and Q-ICS-injected rats ate significantly more (p less than 0.05) IMB diet than saline-injected rats. Intake of IMB diet was not different (p greater than 0.4) between ICS and Q-ICS groups. From these results, it appears that ICS restores intake of IMB through a peripheral component.
Serotonin3 (5-HT3) receptor antagonists (ICS 205-930 and MDL 72222) have been shown to block or ameliorate the anorectic response of the rat to amino acid imbalanced (IMB) diets. Two experiments were conducted to determine whether the effects of these antagonists are mediated through central or peripheral 5-HT3 receptors. In Experiment One, ICS 205-930 (ICS) was injected centrally, into either the lateral ventricle (doses: 0.3 pmol to 10 nmol), or the cisterna magna (62 nmol). The intake of rats fed an isoleucine IMB diet was not affected by these injections. In Experiment Two, rats received an IP injection of either saline, ICS, or a quaternized derivative of ICS (Q-ICS) that should not cross the blood-brain barrier. Both ICS- and Q-ICS-injected rats ate significantly more (p less than 0.05) IMB diet than saline-injected rats. Intake of IMB diet was not different (p greater than 0.4) between ICS and Q-ICS groups. From these results, it appears that ICS restores intake of IMB through a peripheral component.