Calcitonin-induced anorexia in rats: evidence for its inhibitory action on lateral hypothalamic chemosensitive neurons.
Effects of a synthetic derivative of eel calcitonin, [Asu1,7]ECT on feeding behavior, and its direct action on the neuronal activity of lateral hypothalamic area (LHA) were studied in rats. Food intake was significantly reduced in a dose-dependent manner after intra-third ventricular injection of [Asu1,7]ECT (0.2-1.0 U/rat). The neuronal activity of LHA neurons, especially the glucose-sensitive neurons, was inhibited by electrophoretic application of [Asu1,7]ECT. The inhibition was accompanied by a hyperpolarization of the membrane by about 5-7 mV with an increase in the membrane resistance (5.0-8.7%). This effect was also shown to be independent of noradrenergic or serotonergic mechanisms. Phosphodiesterase inhibitors, such as 3-isobutyl-1-methylxanthine and papaverine augmented the inhibitory response, whereas nicotinic acid blocked it. These results suggest that the anorexia caused by [Asu1,7]ECT is mediated through a direct inhibition of chemosensitive neuronal activity in the LHA, caused by an increase in the intracellular level of cyclic 3',5'-adenosine monophosphate.
Shimizu
N
N
Oomura
Y
Y
D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003864:Depression, Chemical; D004347:Drug Interactions; D005247:Feeding Behavior / Q000187:drug effects*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects*; D008297:Male; D009525:Niacin / Q000008:administration & dosage; D009638:Norepinephrine / Q000008:administration & dosage; D010208:Papaverine / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000008:administration & dosage
D009525:Niacin; D012701:Serotonin; D002116:Calcitonin; D010208:Papaverine; D015056:1-Methyl-3-isobutylxanthine; C012755:elcatonin; D009638:Norepinephrine