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. 1991 Mar;102(3):635–638. doi: 10.1111/j.1476-5381.1991.tb12225.x

Pharmacology of a cholecystokinin receptor on 5-hydroxytryptamine neurones in the dorsal raphe of the rat brain.

P R Boden 1, G N Woodruff 1, R D Pinnock 1
PMCID: PMC1917942  PMID: 1364831

Abstract

1. The effect of bath application of sulphated cholecystokinin octapeptide (CCK-8) was studied on neurones in slices containing rat raphe nucleus. 2. Intracellular recordings were made from neurones in the dorsal raphe nucleus. Some of the neurones with the characteristics of 5-hydroxytryptamine (5-HT)-containing cells which were inhibited by 5-HT and excited by noradrenaline were excited by cholecystokinin. The response to cholecystokinin was dose-dependent over the range 10 to 1000 nM. 3. The response to CCK-8 persisted in the presence of tetrodotoxin. Either reduction of extracellular calcium or addition of 25 mM magnesium did not block the CCK response, suggesting it was mediated by receptors located on the membrane of the raphe neurones. 4. The agonist and antagonist specificity of the CCK response was determined. The CCKB selective agonist, pentagastrin, was inactive when applied at concentrations up to 10 microM. the CCKA receptor antagonist L-364,718 (1 to 100 nM) blocked the response to cholecystokinin. Much higher (1-10 microM) concentrations of the CCKB receptor antagonist L-365,260 were required for inhibition of the CCK response. 5. These data support the existence of a CCK receptor, located on raphe neurones in the rat, with a pharmacological profile very similar to that described for the CCKA type.

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Selected References

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  1. Aghajanian G. K., Lakoski J. M. Hyperpolarization of serotonergic neurons by serotonin and LSD: studies in brain slices showing increased K+ conductance. Brain Res. 1984 Jul 2;305(1):181–185. doi: 10.1016/0006-8993(84)91137-5. [DOI] [PubMed] [Google Scholar]
  2. Aghajanian G. K. Modulation of a transient outward current in serotonergic neurones by alpha 1-adrenoceptors. Nature. 1985 Jun 6;315(6019):501–503. doi: 10.1038/315501a0. [DOI] [PubMed] [Google Scholar]
  3. Baraban J. M., Aghajanian G. K. Noradrenergic innervation of serotonergic neurons in the dorsal raphe: demonstration by electron microscopic autoradiography. Brain Res. 1981 Jan 5;204(1):1–11. doi: 10.1016/0006-8993(81)90646-6. [DOI] [PubMed] [Google Scholar]
  4. Boden P., Hill R. G. Effects of cholecystokinin and related peptides on neuronal activity in the ventromedial nucleus of the rat hypothalamus. Br J Pharmacol. 1988 May;94(1):246–252. doi: 10.1111/j.1476-5381.1988.tb11521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang R. S., Lotti V. J. Biochemical and pharmacological characterization of an extremely potent and selective nonpeptide cholecystokinin antagonist. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4923–4926. doi: 10.1073/pnas.83.13.4923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dodd J., Kelly J. S. The actions of cholecystokinin and related peptides on pyramidal neurones of the mammalian hippocampus. Brain Res. 1981 Feb 2;205(2):337–350. doi: 10.1016/0006-8993(81)90344-9. [DOI] [PubMed] [Google Scholar]
  7. Hill D. R., Campbell N. J., Shaw T. M., Woodruff G. N. Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists. J Neurosci. 1987 Sep;7(9):2967–2976. doi: 10.1523/JNEUROSCI.07-09-02967.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hill D. R., Shaw T. M., Dourish C. T., Woodruff G. N. CCK-A receptors in the rat interpeduncular nucleus: evidence for a presynaptic location. Brain Res. 1988 Jun 28;454(1-2):101–105. doi: 10.1016/0006-8993(88)90807-4. [DOI] [PubMed] [Google Scholar]
  9. Lotti V. J., Chang R. S. A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK-B) ligand: L-365,260. Eur J Pharmacol. 1989 Mar 21;162(2):273–280. doi: 10.1016/0014-2999(89)90290-2. [DOI] [PubMed] [Google Scholar]
  10. Marshall F. H., Barnes S., Pinnock R. D., Hughes J. Characterization of cholecystokinin octapeptide-stimulated endogenous dopamine release from rat nucleus accumbens in vitro. Br J Pharmacol. 1990 Apr;99(4):845–848. doi: 10.1111/j.1476-5381.1990.tb13018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pan Z. Z., Colmers W. F., Williams J. T. 5-HT-mediated synaptic potentials in the dorsal raphe nucleus: interactions with excitatory amino acid and GABA neurotransmission. J Neurophysiol. 1989 Aug;62(2):481–486. doi: 10.1152/jn.1989.62.2.481. [DOI] [PubMed] [Google Scholar]
  12. Vanderhaeghen J. J., Lotstra F., De Mey J., Gilles C. Immunohistochemical localization of cholecystokinin- and gastrin-like peptides in the brain and hypophysis of the rat. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1190–1194. doi: 10.1073/pnas.77.2.1190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Williams J. T., Colmers W. F., Pan Z. Z. Voltage- and ligand-activated inwardly rectifying currents in dorsal raphe neurons in vitro. J Neurosci. 1988 Sep;8(9):3499–3506. doi: 10.1523/JNEUROSCI.08-09-03499.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Yoshimura M., Higashi H. 5-Hydroxytryptamine mediates inhibitory postsynaptic potentials in rat dorsal raphe neurons. Neurosci Lett. 1985 Jan 7;53(1):69–74. doi: 10.1016/0304-3940(85)90099-0. [DOI] [PubMed] [Google Scholar]
  15. van der Kooy D., Hunt S. P., Steinbusch H. W., Verhofstad A. A. Separate populations of cholecystokinin and 5-hydroxytryptamine-containing neuronal cells in the rat dorsal raphe, and their contribution to the ascending raphe projections. Neurosci Lett. 1981 Oct;26(1):25–30. doi: 10.1016/0304-3940(81)90420-1. [DOI] [PubMed] [Google Scholar]

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