Bombesin was described in 1970, as a tetradecapeptide in the skin of frogs (Bombina bombina). Although Bombesin itself does not exist in mammalian tissue, peptides with structural homology to bombesin (Bombesin Like Peptides) were identified in mammals. The mammalian homologues described were Gastrin Releasing Peptide (GRP)  Biochem Biophys Res Commun. 1979 Sep 12;90(1):227-33.   and Neuromedin B, (NMB); Biochem Biophys Res Commun. 1983 Jul 29;114(2):541-8.   Several forms of both these have also been described including GRP _18-27 (Neuromedin C), Ann N Y Acad Sci. 1988;547:373-90.   GRP _1-27,    NMB _1-32,     NMB _2-32,     NMB _23-32.  Three  Bombesin Like Peptide (BNLP) receptors have been described, namely GRP receptor (GRP-R),    NMB receptor (NMB-R), Trends Neurosci. 1991 Dec;14(12):524-8.  and Bombesin receptor subtype 3 (BRS-3).   Eur J Biochem. 1992 Sep 1;208(2):405-10.   Bombesin has affinity for both GRP receptor as well as NMB receptor.  An endogenous ligand for the BRS-3 receptor awaits characterisation. The GRP gene is located on chromosome 18. GRP is produced  from pre-pro-GRP. 

Effects of BNLP administration

Infusion of Bombesin preserves normal meal initiation in rats, but induces a dose dependent early satiety. Life Sci. 1985 Jul 15;37(2):147-53.     In humans, Bombesin Am J Physiol. 1993 Feb;264(2 Pt 2):R350-4.   or GRP Gastroenterology. 1994 May;106(5):1168-73.  infusion induced a reduction in hunger with early satiety with minimal side effects. Both peripheral and central administration of BNLPs induces feeding suppression, with greater potency on central administration.  Bombesin is more potent than GRP in producing anorexia when administered centrally, with NMB_23-32 being least potent. Neuropeptides. 1999 Oct;33(5):376-86.    The potency of Bombesin over the BNLPs is attributed to the amidated terminal which makes it more resistant to enzymatic degradation.

The Nucleus of tractus solitarius and DMV (dorsal motor nucleus of vagus) shows dense population by neurons immunoreactive for bombesin. J Comp Neurol. 1996 Jun 10;369(4):552-70   Bombesin is most effective when infused into the Nucleus of tractus solitarius. Peptides. 1988;9 Suppl 1:245-56. rather than into the 4^th ventricle.  Destruction of the nucleus of tractus solitarius abolishes the effect of Bombesin injected into the 4^th ventricle, while reducing the effect of systemically administered Bombesin. Am J Physiol. 1993 Jun;264(6 Pt 2):R1229-34  Peripheral and central administration of Bombesin evokes  c-Fos-IR activation in the PVN, Nucleus of tractus solitarius and the amygdala.  Regul Pept. 1996 Apr 23;62(2-3):167-72.   The central nucleus of amygdala is being increasingly recognised to be important in ingestive responses with direct projections from the  nucleus of amygdala to the PVN being described. J Comp Neurol. 1984 Mar 20;224(1):1-24.

Interestingly studies in decerebrate rats show that bombesin infusion into the 4th ventricle still produces suppression of food intake. Behav Neurosci. 1992 Dec;106(6):1011-4.   This may mean that the caudal brain stem afferent signals from Bombesin administered in the 4th ventricle are locally integrated, independent of forebrain systems the function of which might be initiation and translation of satiety signals.

Bombesin Like peptides are present in both the gut and  brain. This could potentially facilitate gut-brain communication for satiety signals, possibly mediated through blood brain barrier deficient areas like the area postrema, as BNLPs do not not readily cross the blood brain barrier. Methods Enzymol. 1989;168:652-60. Vagotomy does not attenuate the anorectic effects of systemically administered Bombesin   Am J Physiol. 1997 Jun;272(6 Pt 2):R1726-33.   although more extensive neural disconnection reduced the anorectic action of bombesin. Peptides. 1985 Nov-Dec;6(6):1249-52.  On a similar note, studies using capsaicin (a neurotoxin that specifically blocks sensory afferent- but not efferent- vagal and spinal fibres) demonstrated total unresponsiveness to systemically administered Bombesin with preserved responsiveness to centrally administered bombesin. Am J Physiol. 1999 Jun;276(6 Pt 2):R1617-22.

Effects of Bombesin blockade

Peripheral administration of Bombesin antagonists blocked the effects of peripherally administered Bombesin   Pharmacol Biochem Behav. 1994 Jul;48(3):809-11.    while the actions of centrally administered Bombesin was not blocked. In contrast, central blockade using receptor antagonists or Bombesin antiserum, resulted in blockade of both centrally and peripherally administered Bombesin. Thus peripheral BNLP seems to require central Bombesin-responsive receptors to produce meal suppression. Central GRP and NMB receptor antisense infusion also blocks the effects of exogenously administered bombesin. Soc neurosci Abst 1996; 22:456 

Administration of Bombesin antagonist centrally prolongs meal duration in partially sated animals. Soc Neurosci Abst 1990; 16:978  This may suggest the physiological relevance of Bombesin related mechanism in mediating satiety under normal circumstances.

Effects of receptor deficiency

Mice lacking GRP receptor Biochem Biophys Res Commun. 1997 Oct 9;239(1):28-33.    or NMB receptor J Neurosci. 1999 Feb 1;19(3):948-54.   do not show abnormalities in feeding behaviour, while mice lacking the BRS-3 receptor develop obesity. Nature. 1997 Nov 13;390(6656):165-9.   Bombesin, Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3188-92.   GRP or NMB J Endocrinol. 2002 Aug;174(2):273-81. do not suppress feeding in mice lacking the GRP receptor.

In contrast to most gut hormones, Bombesin related peptides have the potential to increase the inter meal interval if administered in between meals, Peptides. 1998;19(8):1439-42.    apart from merely decreasing meal size when administered during meals.

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