Different types of bombesin receptors on neurons in the dorsal raphe nucleus and the rostral hypothalamus in rat brain slices in vitro.
The actions of the peptides bombesin (BN), gastrin releasing peptide (GRP), neuromedin C (NMC), litorin and neuromedin B (NMB) were studied on neurons in slices of rat brain maintained in vitro to determine the BN receptor type present in different brain areas. Intracellular and extracellular recordings were made from hypothalamic neurons on the border of the periventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) and from mesencephalic 5-HT sensitive neurons in the dorsal raphe nucleus. In the region of the brain containing the SCN and PVN, BN and the BN-related peptides excited 31 out of 77 neurons on which they were tested. There was little difference in the potency of the BN-related peptides as excitants of neurons, the EC50 being about 10 nM. The response to the peptides usually lasted between 5 and 15 min with little sign of desensitization. Using NMC, GRP and NMB as agonists, the equilibrium constant for the GRP receptor antagonist [D-Phe6]-BN-(6-13)-ethylamide was approximately 10 nM. The response to the peptides fully recovered on washout of the antagonist. The CCKB/gastrin receptor antagonist CI-988 (1 microM) had no effect on either GRP- or NMC-mediated excitation. In the dorsal nucleus 40 of 75 neurons were sensitive to the BN-related peptides. BN, [Tyr4]-BN, NMB and litorin, were 10-20 times more potent than GRP and NMC. The responses to the BN-related peptides were not blocked by the selective GRP receptor antagonists [D-Phe6]-BN-(6-13)-methylester, [DF5Phe6][D-Ala11]-BN-(6-13)-methylester and [D-Phe6]-BN-(6-13)- ethylamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Pinnock
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RD
Parke Davis Neuroscience Research Unit, Addenbrookes Hospital Site, Cambridge, UK.
Reynolds
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T
Woodruff
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GN
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects
D009479:Neuropeptides; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C090718:bombesin (6-13)-ethylamide, Phe(6)-; D001839:Bombesin