CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents.
Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.
van de Wall
E H E M
EH
Dept. of Neuroendocrinology, University of Groningen, PO Box 14, 9750 AA Haren, The Netherlands.
Duffy
P
P
Ritter
R C
RC
D000818:Animals; D031608:Area Postrema / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002404:Catheterization; D002766:Cholecystokinin / Q000494:pharmacology*; D004351:Drug Resistance; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism; D017552:Solitary Nucleus / Q000378:metabolism; D013270:Stomach / Q000187:drug effects* / Q000502:physiology*; D014018:Tissue Distribution; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos; D002766:Cholecystokinin; D002211:Capsaicin