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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 May;94(1):246–252. doi: 10.1111/j.1476-5381.1988.tb11521.x

Effects of cholecystokinin and related peptides on neuronal activity in the ventromedial nucleus of the rat hypothalamus.

P Boden 1, R G Hill 1
PMCID: PMC1853924  PMID: 3401640

Abstract

1. An investigation into the effects of cholecystokinin octapeptide (CCK-8S) and its pentapeptide analogue, pentagastrin, on neurones located in ventromedial nuclei of rat hypothalamic slices maintained in vitro has been undertaken. 2. CCK-8S (0.01-1.0 microM) applied in the perfusion medium produced a concentration-dependent increase in firing rate. This effect could be mimicked by pentagastrin and was selectively blocked by L-364,718, a potent peripheral CCK receptor antagonist that has been shown to possess micromolar affinity for central CCK receptors. 3. Intracellular recordings from ventromedial nucleus neurons revealed two distinct populations with comparable resting membrane parameters but differing neuronal activity. One group fired tetrodotoxin (TTX)-sensitive action potentials spontaneously at resting membrane potential whilst the second group fired action potentials only on injection of depolarizing current and were otherwise silent. 4. Application of CCK-8S or pentagastrin to spontaneously active neurones produced a small depolarization concomitant with an increase in action potential firing rate but the peptides had no effect on membrane properties of 'silent' neurones. 5. These data suggest the existence of at least two populations of neurones in the ventromedial hypothalamus, only one of which is excited by CCK-8S and pentagastrin.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Clark C. R., Daum P., Hughes J. A study of the cerebral cortex cholecystokinin receptor using two radiolabelled probes: evidence for a common CCK 8 and CCK 4 cholecystokinin receptor binding site. J Neurochem. 1986 Apr;46(4):1094–1101. doi: 10.1111/j.1471-4159.1986.tb00623.x. [DOI] [PubMed] [Google Scholar]
  3. Day N. C., Hall M. D., Clark C. R., Hughes J. High concentrations of cholecystokinin receptor binding sites in the ventromedial hypothalamic nucleus. Neuropeptides. 1986 Jul;8(1):1–18. doi: 10.1016/0143-4179(86)90059-4. [DOI] [PubMed] [Google Scholar]
  4. Fulwiler C. E., Saper C. B. Cholecystokinin-immunoreactive innervation of the ventromedial hypothalamus in the rat: possible substrate for autonomic regulation of feeding. Neurosci Lett. 1985 Feb 4;53(3):289–296. doi: 10.1016/0304-3940(85)90553-1. [DOI] [PubMed] [Google Scholar]
  5. Haller E. W., Wakerley J. B. Electrophysiological studies of paraventricular and supraoptic neurones recorded in vitro from slices of rat hypothalamus. J Physiol. 1980 May;302:347–362. doi: 10.1113/jphysiol.1980.sp013247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hatton G. I., Armstrong W. E., Gregory W. A. Spontaneous and osmotically-stimulated activity in slices of rat hypothalamus. Brain Res Bull. 1978 Sep-Oct;3(5):497–508. doi: 10.1016/0361-9230(78)90079-5. [DOI] [PubMed] [Google Scholar]
  7. Hatton G. I., Doran A. D., Salm A. K., Tweedle C. D. Brain slice preparation: hypothalamus. Brain Res Bull. 1980 Jul-Aug;5(4):405–414. doi: 10.1016/s0361-9230(80)80010-4. [DOI] [PubMed] [Google Scholar]
  8. Inenaga K., Yamashita H. Excitation of neurones in the rat paraventricular nucleus in vitro by vasopressin and oxytocin. J Physiol. 1986 Jan;370:165–180. doi: 10.1113/jphysiol.1986.sp015928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kow L. M., Pfaff D. W. CCK-8 stimulation of ventromedial hypothalamic neurons in vitro: a feeding-relevant event? Peptides. 1986 May-Jun;7(3):473–479. doi: 10.1016/0196-9781(86)90017-3. [DOI] [PubMed] [Google Scholar]
  10. Kow L. M., Pfaff D. W. Suprachiasmatic neurons in tissue slices from ovariectomized rats: electrophysiological and neuropharmacological characterization and the effects of estrogen treatment. Brain Res. 1984 Apr 16;297(2):275–286. doi: 10.1016/0006-8993(84)90568-7. [DOI] [PubMed] [Google Scholar]
  11. Madison D. V., Nicoll R. A. Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro. J Physiol. 1984 Sep;354:319–331. doi: 10.1113/jphysiol.1984.sp015378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Millhouse O. E. Certain ventromedial hypothalamic afferents. Brain Res. 1973 May 30;55(1):89–105. doi: 10.1016/0006-8993(73)90490-3. [DOI] [PubMed] [Google Scholar]
  13. Millhouse O. E. The organization of the ventromedial hypothalamic nucleus. Brain Res. 1973 May 30;55(1):71–87. [PubMed] [Google Scholar]
  14. Minami T., Oomura Y., Sugimori M. Electrophysiological properties and glucose responsiveness of guinea-pig ventromedial hypothalamic neurones in vitro. J Physiol. 1986 Nov;380:127–143. doi: 10.1113/jphysiol.1986.sp016276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Minami T., Oomura Y., Sugimori M. Ionic basis for the electroresponsiveness of guinea-pig ventromedial hypothalamic neurones in vitro. J Physiol. 1986 Nov;380:145–156. doi: 10.1113/jphysiol.1986.sp016277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Murphy J. T., Renaud L. P. Mechanisms of inhibition in the ventromedial nucleus of the hypothalamus. J Neurophysiol. 1969 Jan;32(1):85–102. doi: 10.1152/jn.1969.32.1.85. [DOI] [PubMed] [Google Scholar]
  17. Oomura Y., Ooyama H., Yamamoto T., Naka F., Kobayashi N., Ono T. Neuronal mechanism of feeding. Prog Brain Res. 1967;27:1–33. doi: 10.1016/S0079-6123(08)63091-5. [DOI] [PubMed] [Google Scholar]
  18. Pan J. T., Kow L. M., Pfaff D. W. Single-unit activity of hypothalamic arcuate neurons in brain tissue slices. Effects of anterior pituitary hormones, cholecystokinin-octapeptide, and neurotransmitters. Neuroendocrinology. 1986;43(2):189–196. doi: 10.1159/000124527. [DOI] [PubMed] [Google Scholar]
  19. Sutin J., Eager R. II. Anatomical substrates and electrophysiological properties of neural systems regulating food and water intake. Fiber degeneration following lesions in the hypothalamic ventromedial nucleus. Ann N Y Acad Sci. 1969 May 15;157(2):610–628. doi: 10.1111/j.1749-6632.1969.tb12910.x. [DOI] [PubMed] [Google Scholar]
  20. Záborszky L., Beinfeld M. C., Palkovits M., Heimer L. Brainstem projection to the hypothalamic ventromedial nucleus in the rat: a CCK-containing long ascending pathway. Brain Res. 1984 Jun 15;303(2):225–231. doi: 10.1016/0006-8993(84)91208-3. [DOI] [PubMed] [Google Scholar]

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