Role of capsaicin-sensitive peripheral sensory neurons in anorexic responses to intravenous infusions of cholecystokinin, peptide YY-(3–36), and glucagon-like peptide-1 in rats

Abstract

Cholecystokinin (CCK)-induced suppression of feeding is mediated by vagal sensory neurons that are destroyed by the neurotoxin capsaicin (CAP). Here we determined whether CAP-sensitive neurons mediate anorexic responses to intravenous infusions of gut hormones peptide YY-(3-36) [PYY-(3-36)] and glucagon-like peptide-1 (GLP-1). Rats received three intraperitoneal injections of CAP or vehicle (VEH) in 24 h. After recovery, non-food-deprived rats received at dark onset a 3-h intravenous infusion of CCK-8 (5, 17 pmol·kg⁻¹·min⁻¹), PYY-(3-36) (5, 17, 50 pmol·kg⁻¹·min⁻¹), or GLP-1 (17, 50 pmol·kg⁻¹·min⁻¹). CCK-8 was much less effective in reducing food intake in CAP vs. VEH rats. CCK-8 at 5 and 17 pmol·kg⁻¹·min⁻¹ reduced food intake during the 3-h infusion period by 39 and 71% in VEH rats and 7 and 18% in CAP rats. In contrast, PYY-(3-36) and GLP-1 were similarly effective in reducing food intake in VEH and CAP rats. PYY-(3-36) at 5, 17, and 50 pmol·kg⁻¹·min⁻¹ reduced food intake during the 3-h infusion period by 15, 33, and 70% in VEH rats and 13, 30, and 33% in CAP rats. GLP-1 at 17 and 50 pmol·kg⁻¹·min⁻¹ reduced food intake during the 3-h infusion period by 48 and 60% in VEH rats and 30 and 52% in CAP rats. These results suggest that anorexic responses to PYY-(3-36) and GLP-1 are not primarily mediated by the CAP-sensitive peripheral sensory neurons (presumably vagal) that mediate CCK-8-induced anorexia.

A Novel CCK-8/GLP-1 Hybrid Peptide Exhibiting Prominent Insulinotropic, Glucose-Lowering, and Satiety Actions With Significant Therapeutic Potential in High-Fat–Fed Mice

“…In relation to this, vagal afferents coexpress CCK 1 and GLP-1 receptors (26) and might represent a target synergistic interaction between the two hormones. Moreover, it has been suggested that the effects of CCK and GLP-1 on the central regulation of food intake operate via different but complementary autonomic circuits (27)(28)(29). Tolerability and induction of nausea have previously been suggested as important limiting factors in the development of CCK 1 receptor-activating drugs (30).…”

Exogenous glucagon-like peptide-1 acts in sites supplied by the cranial mesenteric artery to reduce meal size and prolong the intermeal interval in rats

“…(7) Reduction of food intake by ip injection of GLP-1 (7–36) was attenuated by total subdiaphragmatic vagotomy (Abbott, et al, 2005). Finally, hepatic portal vein (HPV) and ip infusions of 10 nmol/kg GLP-1 reduced meal size similarly in sham-operated rats, but only HPV GLP-1 reduced meal size in subdiaphragmatic vagal deafferentation rats (Rüttiman et al, 2009) and selective vagal deafferentation (Rüttiman et al, 2009; Hayes et al, 2011), although not by selective or common hepatic branch vagotomy (Hayes, et al, 2011; Ruttimann, et al, 2009) or capsaicin treatment (Reidelberger, Haver, Anders, & Apenteng, 2014; Zhang & Ritter, 2012). …”

“…al. (Reidelberger, et al, 2014), who found that reduction of food intake by 3 h jugular infusion of GLP-1 was not attenuated by capsaicin pretreatment. A possible resolution to this apparent discrepancy may be that capsaicin nonselectively lesions both vagal and non-vagal, small, unmyelinated sensory neurons, but does not lesion myelinated vagal fibers (Gamse, 1982).…”

Mechanisms for the cardiovascular effects of glucagon-like peptide-1

“…), at least this response is not mediated by the capsaicin‐sensitive peripheral sensory neurones in rats (Reidelberger et al . ).…”