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 bo rder of the periventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) and from mesencephalic 5-HT sensitive neurons in the dorsal raph e nucleus. In the region of the brain containing the SCN and PVN, BN a nd 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-rela ted peptides as excitants of neurons, the EC(50) being about 10 nM. Th e response to the peptides usually lasted between 5 and 15 min with li ttle sign of desensitization. Using NMC, GRP and NMB as agonists, the equilibrium constant for the GRP receptor antagonist [D-Phe(6)]-BN-(6- 13)-ethylamide was similar to 10 nM. The response to the peptides full y recovered on washout of the antagonist. The CCKB/gastrin receptor an tagonist CI-988 (1 mu M) had no effect on either GRP- or NMC-mediated excitation. In the dorsal raphe nucleus 40 of 75 neurons were sensitiv e to the BN-related peptides. BN, [Tyr(4)]-BN, NMB and litorin, were 1 0-20 times more potent than GRP and NMC. The responses to the BN-relat ed peptides were not blocked by the selective GRP receptor antagonists [D-Phe(6)]-BN-(6-13)-methylester, [DF5Phe(6)][D-Ala(11)]-BN-(6-13)-me thylester and [D-Phe(6)]-BN-(6-13)- ethylamide. These results suggest that the PVN and SCN contain a population of neurons expressing GRP re ceptors whilst in the dorsal raphe the majority of BN receptors expres sed are of the NMB subtype.