An Overview of the Biological Actions and Neuroendocrine Regulation of Growth Hormone
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
Bombesin was initially isolated from amphibian skin222 and later reported to be present in mammalian brain.223 Bombesin is a tetradecapeptide, and its role as a central nervous system neurotransmitter is currently under investigation. Early studies indicated that both intravenous and intracisternal administration of bombesin to steroid-primed male rats produced a considerable rise in plasma growth hormone, although intravenous injection was more effective. However, more recent studies suggest that intracerebroventricular administration of the peptide inhibits both growth hormone secretion and the response to opioid stimulation, possibly as a result of increased somatostatin secretion.224 A possible confounding factor in several studies of the effects of bombesin (as well as other compounds) is that bombesin can increase growth hormone secretion from pituitary cells.225,226
Developments of Radiolabeled Peptides
Marco Chinol, Giovanni Paganelli in Radionuclide Peptide Cancer Therapy, 2016
Bombesin (BBN), a 14-amino acid peptide (Fig. 13A), originally isolated from frog skin, has a high affinity for gastrin releasing peptide receptor (GRPR). Bombesin belongs to a peptide family, which includes GRP, a 27-amino acid (Fig. 13B) and Neuromedin B, a 10-amino acid peptide (Fig. 13C) derived from pig tissue. These neuropeptides/growth factors have receptors that are normally present in the CNS, GI tract, and pancreas. Bombesin, as well as its related peptides, stimulates the muscles of the GI tract, pancreatic enzymes and GI hormone secretion, and proliferation of rat andrenocortical cells. GRPR are overexpressed in a variety of cancers and their activation stimulates both cell growth and proliferation (Table 1). Bombesin agonists also appear to function as paracrine/autocrine growth stimulators for tumor cells in culture (24,108). Studies with these receptors as targets have been performed mostly in cultured cells or with animal models and limited human studies. A number of groups are examining different analogs (24,107–110).
Parasympathomimetic Amines
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Ach also modulates gastric acid secretion indirectly through other endogenous secretogogues. It increases the release of a neuropeptide of the bombesin family (gastrin releasing peptide, GRP). Bombesin-like immunoreactivity has been identified in the myenteric neurones of the mammalian gastrointestinal tract and bombesin causes marked increases in acid secretion and motility. Bombesin stimulates gastrin secretion from the mucosa of the stomach through activation of a BB2 receptor. In contrast, activation of muscarinic receptors causes inhibition of another local peptide, somatostatin. Somatostatin normally exerts inhibitory effects upon the release of several transmitters through stimulation of SS receptors and this includes the release of gastrin. Thus, the Ach-induced inhibition of somatostatin release removes its inhibitory effect on gastrin release, which is in turn raised. As a result, acid secretion is also raised (Figure 8.3) (Makhlouf 1984). Vagal stimulation in the isolated stomach of rodents also appears to induce gastric acid secretion indirectly via histamine release since the response is also sensitive to H2 receptor blockade with tiotidine (Welsh et al. 1994).
Predicting the likelihood of bronchopulmonary dysplasia in premature neonates
Published in Expert Review of Respiratory Medicine, 2019
Patrick A Philpot, Vineet Bhandari
Urine metabolites and have recently been identified in preterm infants who develop BPD. Bombesin-like peptide is produced by neuroendocrine cells in the lung and increased levels precede BPD. Cullen et al. evaluated 132 infants ≤28 weeks GA and analyzed bombesin-like peptide levels over the first 4 days of life and compared it in infants who developed BPD with those who did not [33]. A first urine bombesin-like peptide level greater than 20,000 pg/mg creatinine (12,500 fmol/mg) between postnatal days 1–4 occurred among 54% of the infants who developed BPD (p ≤ 0.001), versus 10% among non-BPD infants (specificity 90%). Multivariable logistic regression analyses revealed that elevated urine bombesin-like peptide levels were associated with BPD (OR 9.9, 95% CI 3.4, 29) (p ≤ 0.001). The authors concluded that elevated bombesin-like peptide levels at 1–4 days after birth are associated with a 10-fold increased risk of developing BPD.
Chronic interstitial lung diseases in children: diagnosis approaches
Published in Expert Review of Respiratory Medicine, 2018
Nadia Nathan, Laura Berdah, Keren Borensztajn, Annick Clement
Neuroendocrine cell hyperplasia of infancy (NEHI) is a non-lethal disease characterized by a tachypnea without respiratory failure in very young infants. The human airway epithelium contains highly specialized pulmonary neuroendocrine cells. These cells are the first specialized epithelial cells to appear in the lung. Their function remains unknown but is hypothysed to act as mechano and chemo-sensors and to secrete amines and vasopeptides such as gastrin-releasing peptide (GRP) or bombesin. As normal bombesin level decreases after mid-gestation, its overexpression in NEHI could be attributed to a non-regression of neuroendocrine cells. Some molecular defects have recently been documented [53–55]. Clinical presentation is typically a respiratory distress with tachypnea that usually evolves spontaneously well [56]. Pseudo-asthmatic presentations have been reported with wheezing and air-trapping [57]. The lung imaging is characterized by geographic ground-glass opacifications mainly in the right middle lobe and the lingula. On lung biopsy, the abnormal histological findings are minor: hyperplasia of neuroendocrine cells within terminal bronchioles documented by bombesin immunohistochemistry; light thickening of the airway smooth muscle; aspecific increase of the alveolar macrophages [58,59].
Ensifentrine (RPL554): an investigational PDE3/4 inhibitor for the treatment of COPD
Published in Expert Opinion on Investigational Drugs, 2019
Mario Cazzola, Luigino Calzetta, Paola Rogliani, Maria Gabriella Matera
The choice of trequinsin as the starting molecule is explained by the fact that in a preclinical study that investigated the effect duration of selective PDE inhibitors, trequinsin demonstrated duration of action considerably longer than that of many other PDE inhibitors when reversed PGF2α-induced contraction of guinea-pig isolated trachea in vitro and bombesin-induced bronchospasm in anaesthetised guinea-pigs in vivo [23].