Cholecystokinin and prostaglandins inhibit responses of vagal afferent activity to systemic administration of nicotine in anesthetized rats.
Systemic administration of nicotine suppresses food intake. Since gastric vagal afferents convey satiation signals to the hypothalamus in response to cholecystokinin, we investigated the possibility that nicotine increases afferent activity of the gastric vagal nerves by stimulating release of cholecystokinin. Furthermore, involvement of prostaglandins in the responses of gastric vagal afferents to nicotine was also investigated because prostaglandins stimulate gastric vagal afferent activity. Experiments were performed in urethane-anesthetized rats. Intravenous administration of 300 microg/kg but not 3 or 30 microg/kg nicotine produced biphasic increases in afferent activity. The maximum of the first increase was reached within 1 min, while that of the second increase was reached 10-15 min after nicotine injection. Pretreatment with MK-329, a type A cholecystokinin receptor antagonist, significantly reduced the first increase, without influencing the second increase. Pretreatment with indomethacin, a cyclooxygenase inhibitor, further reduced the first increase and abolished the second increase. These results suggest that nicotine can exert its anorexic effect via an increase in gastric vagal afferent activity which is caused by enhanced release of both cholecystokinin and prostaglandins.
Kurosawa
Mieko
M
Center for Medical Science, International University of Health and Welfare, 2600-1 Kitakanemaru, Otawara, Tochigi 324-8501, Japan. mieko-ku@iuhw.ac.jp
Taniguchi
Takamichi
T
Yoneda
Masashi
M
D000758:Anesthesia; D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D020109:Devazepide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018738:Hexamethonium / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D017833:Visceral Afferents / Q000187:drug effects* / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D006727:Hormone Antagonists; D018733:Nicotinic Antagonists; D011453:Prostaglandins; D018738:Hexamethonium; D009538:Nicotine; D002766:Cholecystokinin; D020109:Devazepide; D007213:Indomethacin