Inhibitory Effect Of Bombesin Research Articles

Bombesin microinjection into the basolateral amygdala influences feeding behavior in the rat

It has been demonstrated that the basolateral amygdala (ABL) represents a satiety mechanism. Experimental data indicate that peripheral or central applications of neuropeptide bombesin (BN) and BN-like peptides inhibit feeding. Since the amygdala (AMY) is rich in BN-like immunoreactive elements, the present study was performed to determine whether 10 or 40 ng doses of BN microinjected bilaterally into the ABL could modify solid food intake. Twenty nanograms of BN (10 ng per injection site) in 24-h deprived rats caused transient inhibition of food intake and 80 ng resulted in a significant reduction of food consumption for 1 h. This inhibitory effect of BN on feeding was eliminated by prior BN antagonist treatment. Results of behavioral tests showed that BN microinjections into the ABL specifically reduced food intake without altering behavioral patterns or influencing the body temperature. Present results suggest that BN-like peptides may act as a complex satiety signal in the ABL.

Inhibitory effect of bombesin and SMS 201–995 on DNA synthesis in the rat thyroid lobes incubated in vitro

The effects of 4-h incubation in the presence of bombesin on the incorporation of [ 3H]-thymidine into DNA of the rat thyroid lobes, collected from animals treated in vivo with a long-acting somatostatin analog (SMS 201–995) or with 0.9% NaCl, were investigated. It was shown that not only in vivo injections of SMS 201–995, but also, unexpectedly, in vitro incubation with bombesin inhibited [ 3H]-thymidine incorporation. The two examined substances did not reveal any additive action in their inhibitory effects on the thyroid growth.

Somatostatin mediates bombesin inhibition of chloride secretion by rectal gland

The function of bombesin-like peptide, a neurotransmitter present in nerve fibers of elasmobranch rectal glands, is unknown. Since the principal activity of the rectal gland is to secrete chloride, the effects of bombesin on chloride secretion and the role of somatostatin in this response was studied. Bombesin failed to stimulate secretion in rectal glands perfused in the basal state. When added to glands stimulated by a constant infusion of vasoactive intestinal peptide (VIP), bombesin (8 x 10(-7) M) reversibly inhibited chloride secretion by 56 +/- 9.7% and at the same time evoked a 10-fold increase in the liberation of somatostatin into the venous effluent. Inactivation of somatostatin by the addition of cysteamine partially suppressed the inhibitory effect of bombesin on glandular secretion. The effect of bombesin to reduce chloride secretion was completely prevented by the calcium channel blocker nifedipine, which inhibits neurotransmitter release. These results suggest that bombesin inhibits the effect of VIP to stimulate chloride secretion by releasing somatostatin from neurosecretory nerve terminals within the rectal gland.

Intrathecal injection of bombesin inhibits gastric acid secretion in the rat

Bombesin (100–500 ng) injected intrathecally (T9–10) inhibited gastric acid secretion stimulated by pentagastrin and the GABAB agonist baclofen in urethane-anesthetized rats and basal gastric acid secretion in conscious, pylorus-ligated rats. Peptide action was dose-related, occurred within 30 min, and lasted for > 1h. Bombesin-induced inhibition of pentagastrin-stimulated gastric acid secretion was not altered by cervical cord transection. Intravenous infusion of the monoclonal bombesin antibody 2A11 abolished intravenous bombesin (10 μg/kg · h)-induced 33% inhibition of gastric response to pentagastrin but did not alter intrathecal bombesin (200 ng)-induced 38% inhibition of gastric response to pentagastrin. The inhibitory effect of bombesin (200 ng) on pentagastrin-stimulated gastric secretion was reversed by bilateral adrenalectomy or removal of celiac and mesenteric ganglia. Intrathecal injections of rat calcitonin gene-related peptide, neuromedin B, neuromedin U, and the stable substance P analogue (pGlu5, MePhe8, MeGly9)-substance P(5–11) did not alter pentagastrin-stimulated gastric acid secretion. These results demonstrate that bombesin injected into the subarachnoid space of the spinal cord inhibits vagally stimulated and pentagastrinstimulated gastric secretion in rats. Bombesin action is peptide specific, exerted at a spinal site, and expressed through the sympathetic nervous system.

Sympatho-adrenomedullary system mediation of the bombesin-induced central inhibition of gastric acid secretion

Possible mechanisms of the inhibitory effect of bombesin on gastric acid secretion were examined in rats anesthetized with urethane. Intracerebroventricular (i.c.v.) administration of bombesin (0.1–3 nmol) dose dependently inhibited the increase in gastric acid secretion induced by both intravenous (i.v.) administration of 2-deoxy-D-glucose 60 mg/kg and electrical stimulation of the vagus nerve (1 mA, 0.5 ms, 3 Hz), but not increase due to i.v. infusion of bethanechol (10 μg/kg per min). Such an inhibitory effect of bombesin on the gastric response was markedly reduced by bilateral cutting of the greater splanchnic nerves. The inhibitory effect of bombesin on gastric acid secretion induced by stimulation of the vagus nerve was not modified either by chemical sympathectomy with 6-hydroxydopamine or by bilateral adrenalectomy alone. However, this inhibitory effect of bombesin was abolished under conditions of combined chemical sympathectomy and adrenalectomy. These results suggest that bombesin (i.c.v.) probably excites the sympatho-adrenomedullary system and thus induces inhibition of gastric acid secretion. Furthermore, a dysfunction of the sympathetic or of the adrenomedullary system may well be functionally compensated for by the system with unaltered function.

Central Site of Inhibitory Action of Bombesin on Gastric Acid Secretion in Rats

Sites of inhibitory action of bombesin on gastric acid secretion were examined in rats anesthetized with urethane. Intracerebroventricular administration of bombesin (3-1000 pmole) dose-dependently inhibited the increase in gastric acid secretion induced by electrical stimulation of the vagus nerve (1 mA, 0.5 msec, 3 Hz). On the other hand, intrathecal (direct lumbar puncture) administration of bombesin, even in the large dose of 1 nmole, had no effect on the vagally stimulated gastric acid secretion. Three pmoles of bombesin microinjected into the preoptic area, the anterior hypothalamus and the paraventricular nucleus inhibited the vagus stimulated gastric acid secretion. Microinjection of this peptide into the ventromedial nucleus, the dorsomedial nucleus and the lateral hypothalamic area were without effect. A large electrolytic lesion of the anterior hypothalamus, including the preoptic-anterior hypothalamic area and the paraventricular nucleus, abolished the inhibitory effect of intracerebroventricularly applied bombesin, but a lesion restricted to the preoptic-anterior hypothalamus or the paraventricular nucleus was without effect. We propose that the preoptic area, the anterior hypothalamus and the paraventricular nucleus are all involved in the inhibitory effect of bombesin on gastric acid secretion.

Central site of inhibitory action of bombesin on gastric acid secretion in rats.

Sites of inhibitory action of bombesin on gastric acid secretion were examined in rats anesthetized with urethane. Intracerebroventricular administration of bombesin (3-1000 pmole) dose-dependently inhibited the increase in gastric acid secretion induced by electrical stimulation of the vagus nerve (1 mA, 0.5 msec, 3 Hz). On the other hand, intrathecal (direct lumbar puncture) administration of bombesin, even in the large dose of 1 nmole, had no effect on the vagally stimulated gastric acid secretion. Three pmoles of bombesin microinjected into the preoptic area, the anterior hypothalamus and the paraventricular nucleus inhibited the vagus stimulated gastric acid secretion. Microinjection of this peptide into the ventromedial nucleus, the dorsomedial nucleus and the lateral hypothalamic area were without effect. A large electrolytic lesion of the anterior hypothalamus, including the preoptic-anterior hypothalamic area and the paraventricular nucleus, abolished the inhibitory effect of intracerebroventricularly applied bombesin, but a lesion restricted to the preoptic-anterior hypothalamus or the paraventricular nucleus was without effect. We propose that the preoptic area, the anterior hypothalamus and the paraventricular nucleus are all involved in the inhibitory effect of bombesin on gastric acid secretion.

Central inhibitory effect of bombesin on gastric functions in relation to sympatho-adrenomedullarly system

Central inhibitory effect of bombesin on gastric functions in relation to sympatho-adrenomedullarly system

Prolonged Inhibition of Growth Hormone Secretion by Peripheral Injection of Bombesin Is Mediated by Somatostatin in the Rat*

Peripherally injected bombesin inhibits GH secretion in conscious, freely moving rats and in sodium pentobarbital-anesthetized rats. This inhibition of GH secretion is unusually prolonged, lasting up to 90 min after a single ip injection. The duration of inhibition of GH secretion by bombesin is greater than that observed for somatostatin (SRIF) in the same bioassay. The inhibition of GH release occurs concomitantly with stimulation of gastrin release and is independent of stimulatory effects of bombesin on plasma glucose. The structurally related mammalian gastrin-releasing peptide also inhibits GH secretion in the pentobarbital-anesthetized rat after peripheral injection. Peripherally administered bombesin blocks GH-releasing factor stimulation of GH secretion. Prior treatment of pentobarbital-anesthetized rats with SRIF-specific anti-serum blocks the inhibitory effect of bombesin on GH secretion. No effect of bombesin on GH secretion was observed in primary cultures of rat anterior pituitary cells. These data suggest that peripherally administered bombesin stimulates SRIF secretion, most probably of hypothalamic origin, which, in turn, inhibits pituitary secretion of GH. This sensitivity of the hypothalamus to a peripherally rather than centrally administered peptide has important mechanistic and therapeutic implications.

Bombesin inhibits thyrotrophin secretion in rats

The effects of peripheral administration of bombesin on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. Bombesin (200 micrograms/kg) was injected iv, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by radioimmunoassay. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after bombesin injection, whereas plasma concentrations tended to decrease, but not significantly. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. Plasma thyroid hormone levels did not change significantly. Plasma ir-TRH and TSH responses to cold were inhibited by bombesin, but the plasma TSH response to TRH was not affected. In the pimozide- or para-chlorophenylalanine pre-treated group, the inhibitory effect of bombesin on TSH levels was prevented, but not in the L-Dopa- or 5-hydroxytryptophan pre-treated group. These drugs alone had no effect on plasma TSH levels in terms of the dose used. The inactivation of TRH immunoreactivity in plasma or hypothalamus in vitro after bombesin injection did not differ from that of the controls. These findings suggest that bombesin acts on the hypothalamus to inhibit TRH release, and that its effects are at least partially modified by amines of the central nervous system.