Alan [corrected] N. Epstein award: Intracellular signaling and ingestive behaviors

Abstract

Understanding the role of intracellular signaling pathways in ingestive behavior is a challenging problem in behavioral neuroscience. This review summarizes work conducted on two systems with the aim of identifying intracellular events that relate to food and fluid intake. The first set of experiments focused on melanocortin receptors and their ability to signal through members of the mitogen-activated protein (MAP) kinase family. The second set of experiments focused on the role of intracellular signaling pathways in water and saline intakes that are stimulated by angiotensin II (AngII). The initial findings in each line of research have been extended by subsequent research that is discussed in turn. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.

Figure 1

cAMP and MAP kinase signaling through the melanocortin receptors. COS-1 cells were transfected with MC3 or MC4 receptor and treated with MTII. Formation of cAMP is shown on the left (white bars) and activated (phosphorylated) ^p44/42MAP kinase is shown on the right (black bars). Asterisks are used to indicate differences from cells in the same transfection condition that were treated with vehicle. Based on Daniels et al. [29].

Figure 2

Melanocortin-induced ^p44/42MAP kinase activation in rat PVN. (A) The number of cells immunohistochemically labeled for phosphorylated ^p44/42MAP kinase in brains from rats treated with vehicle or MTII is shown as the mean (±SEM) cells per PVN hemisection). An asterisk indicates p<0.05. (B) Double-labeling for phosphorylated ^p44/42MAP kinase (red) and oxytocin (green) in the brain of a rat injected with MTII. The scale bar is 50 μm. Data are from Daniels et al. [29].

Figure 3

The angiotensin analog, SII, stimulates MAP kinase and saline intake, but antagonizes AngII- formation and water intake. (A) AngII and SII similarly increase activated ^p44/42MAP kinase induced IP₃ in COS-1 cells transfected with the AT₁ receptor. (B) COS-1 cells were transfected with AT₁ receptor and subsequently treated with vehicle (ctrl) or AngII in the presence or absence of SII. SII failed to stimulate IP₃ formation and prevented AngII-induced IP₃ formation. (C) Water intake in a one-bottle test was stimulated by AngII injected into the forebrain ventricle of male rats; however, rats injected with SII did not drink more water than controls and AngII-induced intake was prevented by SII. (D) Rats injected with AngII or SII drank similar volumes of 1.5% saline in a two-bottle test. Asterisks indicate p<0.05 compared to controls. Data are from Daniels et al. [38].

Figure 4

The effect of PKC or MAP kinase inhibition on 60-minute water and saline intakes in response to AngII. Data are shown as the mean SEM intake relative to the average response to AngII alone. PKC inhibition attenuated water, but not saline intake (A), whereas MAP kinase inhibition reduced saline, but not water intake (B). Asterisks are used to intake differences from vehicle-treated or inhibitor-only groups and crosses intake differences from all other treatment groups (p<0.05) using the raw intake data before transformation to percent of mean baseline intakes. Based on Daniels et al. [48].