Capsaicin treatment differentially affects feeding suppression by bombesin-like peptides

Abstract

Peripheral administration of bombesin (BN) and the related mammalian peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), suppress food intake in rats. To examine whether all BNlike peptides utilize the same neural pathways to reduce feeding, rats were treated on postnatal day 2 with the injection vehicle or capsaicin, a neurotoxin that damages a subset of visceral afferent fibers. When rats reached adulthood, we compared the ability of a dose range of systemically administered BN, GRP18-27 and NMB to reduce intake of a 0.5 kcal/ml glucose solution in a short-term feeding test. Our results demonstrate that capsaicin treatment abolished or attenuated the suppression of glucose intake produced by BN and NMB but had no effect on the ability of GRP to reduce feeding. These results suggest that different neural substrates underlie the anorexic effects of peripherally administered BN-like peptides.

International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States

“…Studies comparing the potencies of NMB to GRP as well as binding studies or antagonist studies provide evidence that the BB 1 receptor can stimulate contraction of urogenital and gastrointestinal smooth muscle (esophageal, gastric, colon, and gallbladder) (Regoli et al, 1988;von Schrenck et al, 1989von Schrenck et al, , 1990Severi et al, 1991;Kilgore et al, 1993;Parkman et al, 1994;Milusheva et al, 1998), potently inhibit thyrotropin release from the pituitary gland by acting as an autocrine and paracrine regulator (Rettori et al, 1992;Pazos-Moura et al, 1996;Ortiga-Carvalho et al, 2003), and have potent CNS effects including inhibiting food intake independent of BB 2 stimulation (Ladenheim et al, 1994(Ladenheim et al, , 1996b(Ladenheim et al, , 1997bMerali et al, 1999;Ladenheim and Knipp, 2007) and mediating aspects of the stress and fear responses as well as various behaviors such as spontaneous activity (Merali et al, 2002(Merali et al, , 2006. BB 1 receptor knockout mice are now available and have undergone a limited number of investigations for actions of NMB Oeffner et al, 2000;Yamada et al, 2002bYamada et al, , 2003Yamano et al, 2002) (Table 1).…”

“…In these mice the hypothermic effect of NMB was reduced by 50% without a change in the GRP response, supporting a possible BB 1 receptor-mediated role in thermoregulation: NMB-mediated gastric smooth muscle contraction was not affected, suggesting this is mediated not through BB 1 receptors, and no effect on feeding could be confirmed, although NMB did not have an effect in the control animals (Ohki- . The satiety effects of the BB 1 receptor are mediated through peripheral neural pathways different from those mediating the satiety effects of the BB 2 receptor, because only the satiety effects of BB 1 receptors are inhibited by capsaicin treatment, suggesting the involvement of primary sensory afferent neurons (Ladenheim and Knipp, 2007). Recently, NMB has found to be expressed in human and rodent adipose tissue and to be regulated by changes in energy balance.…”

“…BB 2 receptors are widely expressed in the CNS and in the spinal cord, and numerous central effects have been described with their activation including effects on satiety, regulation of circadian rhythm, thermoregulation, grooming behaviors, modulation of stress, fear, and anxiety response, memory, and gastrointestinal function such as acid secretion (Martinez and Tache, 2000;Yegen, 2003;Moody and Merali, 2004;Karatsoreos et al, 2006;Roesler et al, 2006a,b;Kallingal and Mintz, 2007;Presti-Torres et al, 2007). The satiety effect of BB 2 receptors has been extensively studied (Gibbs et al, 1979;Gibbs and Smith, 1988;Flynn, 1997;Fekete et al, 2007;Ladenheim and Knipp, 2007). A recent study (Ladenheim and Knipp, 2007) showed that the satiety effect of peripherally administered NMB, but not that of GRP, is inhibited by capsaicin pretreatment, suggesting that the neural pathways involved in BB 2 receptor-mediated satiety are either capsaicin-insensitive neurons or involve direct activation of BB 2 receptors in the CNS (Ladenheim and Knipp, 2007).…”

“…The satiety effect of BB 2 receptors has been extensively studied (Gibbs et al, 1979;Gibbs and Smith, 1988;Flynn, 1997;Fekete et al, 2007;Ladenheim and Knipp, 2007). A recent study (Ladenheim and Knipp, 2007) showed that the satiety effect of peripherally administered NMB, but not that of GRP, is inhibited by capsaicin pretreatment, suggesting that the neural pathways involved in BB 2 receptor-mediated satiety are either capsaicin-insensitive neurons or involve direct activation of BB 2 receptors in the CNS (Ladenheim and Knipp, 2007). The importance of BB 2 receptors in mediating the satiety effects of GRP was demonstrated by the ability of a specific BB 2 receptor antagonist administered in the hindbrain of rats to inhibit the satiety effects of peripherally administered GRP (Ladenheim et al, 1996a).…”

“…In the case of the BB 1 receptor such areas include involvement in thyroid function and alterations in thyroid disease Pazos-Moura et al, 2003;Oliveira et al, 2006), behavior effects in mediating aspects of fear, anxiety, and stress responses Merali et al, 2002Merali et al, , 2006Yamada et al, 2003;Bédard et al, 2007); and satiety effects (Merali et al, 1999;Ladenheim and Knipp, 2007). For the BB 2 receptor, such areas include its role in motility with mediation of the descending peristaltic reflex (Grider, 2004) its role in lung injury and development of lung diseases, particularly neonatal lung disease and bronchopulmonary dysplasia, in which Bn-like peptides and the BB 2 receptor were shown to play an important role in various animal models (Li et al, 1994;Sunday et al, 1998;Emanuel et al, 1999;Cullen et al, 2000;Ashour et al, 2006;Ganter and Pittet, 2006;Subramaniam et al, 2007), its role in sepsis and in small intestinal mucosal protection and prevention of injury (Assimakopoulos et al, 2004(Assimakopoulos et al, , 2005aDal-Pizzol et al, 2006;Higuchi et al, 2006;Kimura et al, 2006a,b), its role in satiety effects (Merali et al, 1999;Ladenheim and Knipp, 2007), and its CNS effects on memory, learning, various behaviors, and response to stress (Merali et al, 1999(Merali et al, , 2006Yegen, 2003;Moody and Merali, 2004;Roesler et al, 2004Roesler et al, , 2006ados Santos Dantas et al, 2006;Luft et al, 2006Presti-Torres et al, 2007. For the BB 3 receptor such areas include its possible role in lung development and responses t...…”