Injection Of Bombesin Research Articles

Effects of putative satiety peptides on feeding and drinking behavior in golden hamsters (Mesocricetus auratus).

A series of experiments was conducted to characterize the effects of putative satiety peptides on feeding in the Syrian hamster, a species known to have physiological feeding controls different from those of other animals. Peripheral injections of cholecystokinin octapeptide (CCK-8) reduced feeding in hamsters in a dose-related fashion. CCK-8 was equally effective in reducing food intake in female hamsters tested during the light and dark portions of the illumination cycle but was ineffective in males tested during the light portion. Systemic injections of proglumide, a putative CCK receptor antagonist, did not alter spontaneous food intake and did not reverse the suppression of feeding resulting from peripheral CCK-8 injections. Systemic injections of bombesin (BBS), thyrotropin releasing hormone (TRH), and calcitonin (CT) produced a dose-related suppression of food intake. BBS appeared to do so specifically. In contrast, TRH appeared to reduce feeding by temporarily debilitating the animals; CT, by evoking behavior (increased locomotor activity) incompatible with feeding. Intracerebroventricular (icv) injections of CCK-8, BBS, and CT produced dose-related inhibition of feeding, but only CCK-8 appeared to affect feeding behavior selectively. Reduced feeding after icv BBS was associated with excessive grooming, and icv CT, like systemic CT, increased locomotor behavior. These findings in the hamster are discussed in relation to peptidergic control of feeding in other species.

Effects of gastrointestinal hormones and their related compounds on gastric motility in the rat.

We examined the effects of certain gastrointestinal hormones on gastric motility using rat stomach preparatios in vivo. Changes of water level caused by the movement of the stomach which was filled with saline were recorded. Single injections of cholecystokinin (1, 2 and 4 micrograms/kg) induced relaxation of the stomach. Single injections of bombesin in low doses (below 0.2 microgram/kg) induced relaxation and in high doses (over 0.2 micrograms/kg) contraction after brief relaxation. Single injections of neurotensin (1, 2, 4 and 8 micrograms/kg), somatostatin (5, 10 and 20 micrograms/kg) and substance P (1, 2, 4 and 8 micrograms/kg) induced relaxation followed by contraction, but their dose-response relations were obscure. Infusions of neurotensin (1, 5 and 25 micrograms/kg/h) and somatostatin (2.5 and 5 micrograms/kg/h) enhanced the stomach tension, whereas substance P (1, 5 and 25 micrograms/kg/h) reduced it. Single injections and infusions of neurotensin, somatostatin or substance P showed different effects on gastric motility. On the other hand, Met-enkephalin (1, 10 and 100 micrograms/kg) and porcine motilin (1, 10 and 100 micrograms/kg) did not affect gastric motility in our rat stomach preparations. These results suggest that some gastrointestinal hormones take part in stomach movements.

Bombesin and litorin inhibit ethanol intake

Twenty-three hr water-deprived rats received access to 5% ethanol solution for 30 min daily. Intraperitoneal injection of bombesin (4.0–16.0 μg/kg) or litorin (16.0 μg/kg) significantly inhibited ethanol intake. Litorin (32.0 μg/kg) equivalently suppressed the intakes of 5% ethanol and 8.9% dextrose solutions. The results are consistent with previous reports that administration of bombesin-like peptides selectively inhibits caloric intake in the rat. Injection of bombesin-like peptides may affect ethanol and dextrose intake by eliciting a satiety signal that governs caloric intake.

A role for bombesin in sensory processing in the spinal cord

Bombesin (BN)-containing neuronal processes were demonstrated in laminae I and II of the dorsal horn of the cat, rat, and mouse spinal cord by immunocytochemistry and radioimmunoassay. Dorsal rhizotomy in the cat resulted in a marked decrease in BN immunoreactivity in the dorsal horn indicating that BN is contained in primary sensory afferents. BN-binding sites were also localized in superficial laminae of the dorsal horn. The presence of both BN and BN-binding sites in the dorsal horn suggested that BN may be involved in sensory processing in the spinal cord. Consistent with this hypothesis, it was demonstrated that an injection of BN into the spinal cord caused a biting and scratching response indicative of sensory stimulation. The effect was similar to that observed after injection of substance P into the cord with the exception that the BN effect lasted about 100 times longer than that induced by substance P. Taken together, these data indicate that BN may be a neurotransmitter of primary sensory afferents to the spinal cord.

Increase in neurotensin-like immunoreactivity in rat plasma after administration of calcium, bombesin and fat and its inhibition by somatostatin.

Neurotensin-like immunoreactivity (NTLI) is released from the small intestine into the blood after enteral administration of fat and systemic administration of bombesin. The purpose of the present investigation in the rat was to study the effect of intravenously (i.v.) administered CaCl2 on the plasma concentration of NTLI (p-NTLI) and to investigate the effect of i.v. infusion of somatostatin on basal NTLI release, as well as that stimulated by fat, bombesin and CaCl2. Administration of CaCl2 (5-25 mg X kg-1) increased p-NTLI levels in a significant and dose-dependent manner. In contrast, somatostatin 25-200 ng X min-1) reduced the basal p-NTLI levels, as well as the increase in p-NTLI levels induced by CaCl2 (10 and 25 mg X kg-1), fat (oleic acid, 0.5 ml) and bombesin (25 and 125 pmol X kg-1), in a dose-related manner. Injection of bombesin released immunoreactive material that was indistinguishable from synthetic bovine neurotensin (1-13) upon gel-filtration. This material seemed to be rapidly converted to the more stable metabolite neurotensin (1-8).

Effects of bombesin on body temperature and oxygen consumption in food-deprived rats

The present study measured oxygen consumption and core body temperature following central injections of bombesin (1.0 ug) in food-deprived rats. Oxygen consumption did not differ for bombesin- and control-injected rats while mean core body temperature decreased significantly following bombesin administrations. Present findings suggest seperate mechanisms of heat loss for bombesin-induced hypothermia in cold-exposed and food-deprived rats.

Injections of bombesin into the substantia nigra produce hypothermia and hypophagia in food-deprived rats

Hypothermia and hypophagia have been elicited, under a variety of experimental conditions, by central injections of bombesin. The preoptic area of the anterior hypothalamus has been suggested as the active site for the hypothermia observed in rats exposed to cold, while the lateral hypothalamus has been implicated in the production of hypophagia induced by bombesin. Data are reported here demonstrating a significant, dose-related decrease in both intake of food and body temperature following microinjections of bombesin into the substantia nigra of male rats deprived of food for 18hr. Similar injections into the preoptic area, the lateral hypothalmus and the ventromedial hypothalamus failed to produce a consistent decrease in either intake of food or body temperature. Although a decrease in body temperature was demonstrated following injections into the paraventricular nucleus of the hypothalamus, this decrease did not appear to be dose-related. Injections of bombesin at this site had no effect on food intake. The possibility of an underlying dopaminergic mechanism for the hypothermie and hypophagic effects of bombesin is discussed.

Drinking and feeding inhibition by ICV pulse injection or infusion of bombesin, ranatensin and litorin to rats

The effects on ingestive behavior of the naturally occurring bombesin-like peptides ranatensin and litorin were studied in comparison to those of bombesin by intracerebroventricular pulse injection or by continuous infusion in the rat. Ranatensin and litorin, like bombesin, proved to inhibit drinking and feeding behavior. Marked differences, however, were observed in their effects. In particular our results indicate that these peptides possess different selectivity of action on drinking elicited by different dipsogenic stimuli and different potency and effectiveness in inhibiting food intake induced by food deprivation. Moreover, the effects of the three peptides were markedly affected also by the modality of administration (pulse injection or continuous infusion). On the basis of these results it seems possible to hypothesize that the endogenous bombesin-like peptides may differently affect rat ingestive behavior according to their structure and to the rate and modality of their release in the brain.

Inhibition of satiety by a cholecystokinin antagonist is independent of gastric emptying

The ability of a cholecystokinin antagonist Proglumide to inhibit satiety induced by intraperitoneal injections of cholecystokinin octapeptide (CCK-OP) and bombesin was examined in rats equipped with chronic gastric cannulae. Both CCK-OP and bombesin significantly suppressed sham feeding. Proglumide administered alone did not alter sham feeding but it abolished the suppression of feeding induced by CCK-OP. In contrast. Proglumide did not inhibit the effect of a low dose of bombesin, but partially inhibited satiety induced by a high dose of bombesin, thus confirming our previous findings. These results indicate that the effect of Proglumide is independent of its recently described effects on gastric emptying in rat.

Bombesin increases dopamine function in rat brain areas

Bombesin is a tetradecapeptide heterogenously distributed in the mammalian brain. Bombesin (45 μg) given intracisternally (IC) to unanesthetized rats increased the accumulation of dihydroxyphenylalanine (DOPA) in striatum, olfactory tubercles and hypothalamus after DOPA-decarboxylase inhibition, thus indicating an increased dopamine synthesis. A dose-depdendent increase in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the principal dopamine metabolites, was seen in several brain areas 1 hr after IC injection of bombesin (0–60 μg). In striatum and olfactory tubercles HVA increased more than DOPAC with a maximal increase after 30–45 μg. In a time-course experiment a biphasic change of dopamine metabolites was observed in the olfactory tubercles with an actual decrease in metabolite levels 4 hr after 60 μg IC bombesin injection. Co-administration of bombesin and naloxone (8 mg/kg IP) or ethanol (2.25 g/kg IP) did not affect the increase in dopamine metabolites seen after bombesin alone. The action of IC administered bombesin on dopamine function was most pronounced in hypothalamus indicating a neuroendocrine regulatory function of the peptide.

Lateral hypothalamic mediation of hypergastrinemia induced by intracisternal bombesin.

Electrolytic lesions of the lateral hypothalamus (LH), but not of the lateral thalamus, prevented the elevation of serum gastrin induced by intracisternal injection of bombesin in rats. Knife cuts through the lateral or the posterior LH border largely abolished the rise in circulating gastrin induced by intracisternal bombesin. Cuts through the medial LH border partly inhibited the response, whereas cuts through the anterior LH border did not modify peptide action. None of the transections altered basal gastrin levels nor the rise in gastric pH and inhibition of gastric acid output induced by intracisternal bombesin. LH lesions did not modify the rise in serum gastrin induced by intravenous bombesin. These results demonstrate that the gastrin-releasing effect of intracisternal bombesin requires the integrity of fibers crossing the posterior, lateral, and medial borders of the LH and is independent of changes in gastric pH. The LH area is not itself necessary for the expression of the inhibitory action of bombesin on gastric acid secretion.

Regulation of antral gastrin content.

Five groups of rats were fasted for 3 days and injected with either NaCl or 5, 10, 20, or 40 micrograms/kg bombesin every 8 h. The animals were killed, and their serum and antral gastrin levels were compared with those of normally fed rats. Fasting reduced serum gastrin to 14% of control; antral gastrin was reduced to 21% of control. All doses of bombesin significantly increased serum gastrin in fasted rats, and 20 and 40 micrograms/kg significantly increased antral gastrin. A group of normally fed rats was also compared with one fed a liquid diet for 7 days. Half of each of these was injected with 20 micrograms/kg bombesin (3 times/day) and the other half with NaCl. Bombesin significantly increased serum and antral gastrin in the rats fed solid food. The liquid diet lowered serum and antral gastrin to 17 and 59% of control values, respectively. Bombesin injection totally prevented these decreases. These data indicate that food in the gastrointestinal tract is not required for either gastrin release or synthesis. Furthermore, the data suggest that gastrin synthesis is regulated primarily by gastrin release or by direct stimulation by bombesin rather than by specific food products.

Plasma gonadotropin, prolactin levels and hypothalamic tyrosine hydroxylase activity following intraventricular bombesin and secretin in ovariectomized conscious rats

Plasma gonadotropins, prolactin and hypothalamic tyrosine hydroxylase (TH) activity were evaluated at 15 and 30 min after third ventricular injection of bombesin at doses of 100 or 1000 ng and secretin at dotes of 1000 or 5000 ng in ovariectomized (OVX) unanesthetized rats. Bombesin had no effect on plasma gonadotropin levels. Intraventricular injection of either 100 or 1000 ng dose of bombesin significantly suppressed prolactin levels with parallel elevation in hypothalamic TH activity and there appears to be no dose response relationship. Secretin at 1000 ng dote, significantly lowered plasma LH and PRL levels and elevated hypothalamic TH activity whereas a 5000 ng dose increased PRL concentrations but had no effect on gonadotropin levels and hypothalamic TH activity. Bombesin appears to be a potent inhibitor of PRL release in OVX, conscious rats and this effect may be mediated via hypothalamic dopamine. Lower dose of secretin appears to inhibit PRL release by possibly activating the hypothalamic dopaminergic system, while at higher dose peripheral activation results in enhanced prolactin release.

Chronic bombesin injection can lead to a persistent decrease of food intake and loss of body weight in rats : David B. West, Robert H. Williams, Daren J. Braget and Stephen C. Woods. University of Washington, Seattle, WA. USA

Chronic bombesin injection can lead to a persistent decrease of food intake and loss of body weight in rats : David B. West, Robert H. Williams, Daren J. Braget and Stephen C. Woods. University of Washington, Seattle, WA. USA

Stimulation of gastric secretion by acute lateral hypothalamic lesions and its reversal by intracisternal injection of bombesin

Lateral hypothalamic (LH) but not lateral thalamic (LT) electrolytic lesions markedly increased gastric secretion (volume and acidity) in rats within 2 h of production of the lesions and pylorus ligation. Intracisternal injection of bombesin inhibited gastric secretion (volume and acidity) and reduced to control levels the enhanced acid output produced by the LH lesions. These data demonstrate that acute LH lesions stimulate gastric secretion, and that bombesin exerts a potent gastric antisecretory influence, probably through interaction with LH-related stimulatory pathways.

The effects of injections of bombesin into the cerebral ventricles on food intake and body temperature in food-deprived rats

Central injections of bombesin have been shown to produce hypothermia in animals exposed to a cold environment, but not in animals maintained under thermoneutral conditions. Peripheral injections have been associated with decreased food intake in rats. The data reported here demonstrate a significant, dose-related decrease in both body temperature and food intake following microinjections of bombesin into the cerebral ventricles of male rats maintained at reduced body weight. All measurements of food intake and body temperature were recorded at an ambient temperature of 23 ± 1 °C. The bombesin-induced hypothermia, but not the hypophagia, was partially reversed by prior subcutaneous injections of naloxone. Microinjections of bombesin failed to produce a decrease in body temperature in satiated rats.

Bombesin: Central Nervous System Action to Increase Gastric Mucus in Rats

The effects of intracerebrally applied bombesin on mucus overlying the gastric mucosa surface were quantitatively estimated in rats, using Alcian blue to stain acidic mucus via production of an insoluble dye-mucus complex. In pylorus-ligated rats, intracisternal injection of bombesin increased dye recovery, whereas per os administration of the mucolytic agent N-acetyl-L-cysteine decreased it. The action of intracisternally applied bombesin was rapid in onset, longlasting, dose-dependent with a threshold dose in the range of 50 ng/rat, and specific, as shown by the inactivity of β-endorphin, somatostatin, norepinephrine, serotonin, and dopamine (5–10 μg, given intracisternally). The response to bombesin appeared to be central nervous system-mediated since the peptide was inactive when infused into the jugular vein at 100 ng/min · rat for 1 or 2 h. The effect of the peptide was not modified by indomethacin. Blockade of bombesin-elevated pH did not alter the increase in gastric mucus; other inhibitors of acid secretion, such as atropine, did not influence dye recovery. Acute adrenalectomy, which prevented bombesin-induced hyperglycemia, also completely suppressed the rise in gastric mucus, whereas the action of the peptide on gastric pH remained unaffected. The results of these studies demonstrate that bombesin acts through the brain to increase mucus coating the stomach surface. It also appears that response is not mediated via prostaglandin release, is unrelated to the peptide's inhibitory action on acid secretion, but seems to be adrenal-dependent.

Lateral hypothalamic injection of bombesin decreases food intake in rats

STUCKEY, J. A. AND J. GIBBS. Lateral hypothalamic injection of bombesin decreases food intake in rats. BRAIN RES. BULL. 8(6)617–621, 1982.—The effect of lateral hypothalamic injections of bombesin on feeding behavior was examined. Rats equipped with stainless steel cannulas directed toward the lateral hypothalamus received bilateral injections of bombesin prior to access to a liquid test diet after a 3 hr food deprivation. Bombesin in doses of 5 ng, 50 ng and 100 ng produced significant reductions in the size of the first meal. Injection of 50 ng of the biologically weak analogue [D-Trp 8] bombesin had no effect. Injection of 5 ng or 50 ng of bombesin had no effect on deprivation-induced water intake, and injection of 50 ng of bombesin had no effect on body temperature. The food and water intake data and direct quantitative behavioral measures indicated that lateral hypothalamic injections of bombesin specifically reduced food intake. The structure-activity relationship for this effect was similar to those for other actions of bombesin. A bombesin-like peptide in the lateral hypothalamus or its receptors may play a role in postprandial satiety.

Increased concentration of neurotensin-like immunoreactivity (NTLI) in rat plasma after administration of bombesin and bombesin-related peptides (porcine and chicken gastrin-releasing peptides).

The present experiments in the rat were designed to study the effect of bombesin on plasma concentrations of neurotensin‐like immunoreactivity (NTLI), to localize the gastrointestinal site(s) of bornbesin‐induced NTLI release and to compare the effects of bombesin and mammalian and avian bombesin‐related peptides (porcine and chicken gastrin‐releasing peptides) on the plasma concentrations of NTLI. Tail vein injections of bombesin (7.8–500 pmol X kg‐l) increased plasma NTLI in a dose‐related fashion and a peak concentration was obtained one min after the injection. Bombesin was injected into the arteries supplying certain vascular beds. A significant increase in plasma NTLI was found only after injection into the cranial mesenteric artery—the artery which supplies the intestinal area containing the highest concentration of NTLI. lntralurninal instillation of bombesin (1.25 nmol × kg‐1) into the distal part of the small intestine had no effect upon plasma NTLI. but intraperitoneal injection of bombesin (1.25 nmol × kg‐1) caused a significant increase in plasma NTLI. Intravenous injection of natural porcine and chicken gastrin‐releasing peptides and of synthetic porcine gastrin‐releasing peptide caused similar increases in plasma NTLI as bombesin. Chronic bilateral vagotomy did not change the effect of bombesin on plasma NTLI. The results show that the administration of bombesin and mammalian and avian bombesin‐related peptides markedly elevates the plasma concentration of NTLl in the rat and suggest that this elevation is largely due to release of NTLI from the area of the intestine supplied by the cranial mesenteric artery, i.e. jejunum and ileum.

Inhibition of gastric and pancreatic secretions by cerebroventricular injections of gastrin-releasing peptide and bombesin in rats

It has been suggested that mammalian gastrin-releasing peptide (GRP) and bombesin (BBS) might inhibit gastric secretion by a central nervous system action. The present investigations were intended to define the gastric effect and to look for an effect on the exocrine pancreas. Wistar male rats were provided with a chronic cannula allowing cerebroventricular injections in the 3rd ventricle, and with chronic gastric and/or pancreatic fistulas allowing the collection of gastric and/or pancreatic secretions in conscious animals. Both basal secretions were studied. Gastric secretion was stimulated with a 75 mg/kg s.c. injection of 2-deoxyglucose (2-dGlc). The dose range of bombesin was 0.01–1 μg (6–600 pmol) and GRP was 0.01–10 μg/rat (3.5 pmol to 3.5 nmol). A significant dose related decrease of basal gastric secretion was observed with the two peptides. The gastric acid response to 2-dGlc was inhibited by both peptides in a dose-related fashion and the reduction of gastric acid output mainly resulted from a decrease in the volume of gastric juice. The exocrine pancreatic secretion was also decreased by 30–55% after GRP but the BBS inhibitory effect was poorly dose-related. No significant difference was found after removal of gastric secretion, indicating that most of the pancreatic inhibition was independent of gastric secretion.