Gastric effects of galanin and its interaction with leptin on brainstem neuronal activity.
Galanin is a 29-amino acid peptide that is widely distributed throughout the central nervous system, peripheral nervous system, and gastrointestinal and genitourinary tracts. Leptin is a hormone secreted from adipose tissue and the gut and other tissues. In this study, using an in vitro neonatal rat preparation, we investigated the gastric effects of galanin and its interaction with leptin on nucleus tractus solitarius (NTS) neurons receiving gastric vagal inputs. We showed that peripheral gastric galanin (300 nM) produced a mean inhibition response of 53.2 +/- 2.1% compared with the control level of 100% (P < 0.01) in 27 of 58 neurons tested. A concentration-dependent effect of galanin on NTS neuronal activity was observed. The galanin receptor antagonist [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide], or M40, significantly reversed the galanin-induced inhibition effect (P < 0.01). In contrast, we showed that the peripheral gastric effect of leptin (10 nM) produced a mean activation response of 167.4 +/- 8.2% compared with the control level. The NTS neurons that we recorded could respond to both galanin and leptin or respond to only one of them. Subsequently, we evaluated gastric interactions between galanin and leptin on NTS unitary activity when galanin (100 nM) and leptin (10 nM) were applied together in the gastric compartment. We observed that the effect of leptin when applied alone (168.8 +/- 7.7%) was reduced to 146.2 +/- 4.7% after coapplication of both compounds (P < 0.05 compared with leptin alone; P < 0.01 compared with galanin alone, 55.1 +/- 3.2%). Our data suggest that galanin modulates the leptin signals, which regulate the ingestive process in neonates.
Yuan
Chun-Su
CS
Committee on Clinical Pharmacology, Pritzker School of Medicine, the University of Chicago, Chicago, Illinois, USA. cyuan@midway.uchicago.edu
Dey
Lucy
L
Xie
Jing-Tian
JT
Aung
Han H
HH
D000818:Animals; D001933:Brain Stem / Q000187:drug effects; D004347:Drug Interactions; D019004:Galanin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D013270:Stomach / Q000187:drug effects
D020738:Leptin; D019004:Galanin