Bombesin receptors in the brain.
We have shown that in the central nervous system BN receptors are closely associated with 5-HT systems. On a subpopulation of dorsal raphe neurons, NMB receptors are able to depolarize cells by reducing gK+. In one of the target regions of the dorsal raphe 5-HT neurons, the SCN, we have also shown that neurons are excited by BN-related peptides. In the SCN, the GRP receptors excite neurons by two different mechanisms: closure of gK+ and opening of an unidentified cation conductance. Expression of human BN receptors from the brain in CHO cells or Xenopus oocytes shows a very similar pharmacological profile to that seen in the rat brain slice preparations. In the CHO cell line, following BN receptor activation, a major second-messenger path involves hydrolysis of PIP2 by phospholipases to yield IP3, which releases Ca2+ from intracellular stores. In the oocyte expression system, a similar second messenger pathway is clearly apparent, and Ca2+-sensitive gCl- represents the last phase in a cascade of events. The final phase of the mechanism of action in the artificial systems does not involve gK+, suggesting a different second messenger cascade to that in neurons. However, the involvement of phospholipases and their phospholipid products have not been excluded in neurons.
Woodruff
G N
GN
Parke Davis Neuroscience Research Centre, Cambridge, United Kingdom.
Hall
M D
MD
Reynolds
T
T
Pinnock
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D016384:Consensus Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D018004:Receptors, Bombesin / Q000737:chemistry / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D018004:Receptors, Bombesin; C003291:ranatensin; D012701:Serotonin; D001839:Bombesin; D011761:Pyrrolidonecarboxylic Acid