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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Jul;106(3):697–702. doi: 10.1111/j.1476-5381.1992.tb14397.x

Effects of almitrine on the release of catecholamines from the rabbit carotid body in vitro.

L Almaraz 1, R Rigual 1, A Obeso 1, Y Evrard 1, C Gonzalez 1
PMCID: PMC1907544  PMID: 1504753

Abstract

1. Almitrine increases ventilation by stimulating the carotid body (CB) arterial chemoreceptors but neither its intraglomic target nor its mechanism of action have been elucidated. 2. We have tested the hypothesis that chemoreceptor cells are targets for almitrine by studying its effects on the release of 3H-catecholamines in an in vitro rabbit CB preparation. 3. It was found that almitrine (0.3 and 1.5 x 10(-6) M; i.e. 0.2 and 1 mg ml-1) increases the resting release of 3H-catecholamines from CBs (previously loaded with [3H]-tyrosine) incubated in a balanced 95% O2/5% CO2-equilibrated solution. 4. Almitrine at a concentration of 3 x 10(-6) M (2 mg l-1) also augmented the release of 3H-catecholamines elicited by incubating the CBs in a hypoxic solution (equilibrated with 7% O2/5% CO2 in N2), by high external K+ (35 mM) and by veratridine (2 x 10(-5) M), but did not modify release induced by dinitrophenol (7.5 x 10(-5) M). 5. At the same concentration (3 x 10(-6) M), almitrine increased the rate of dopamine synthesis and was ineffective in modifying the cyclic AMP levels in either normoxic or hypoxic CBs. 6. It is concluded that chemoreceptor cells are the intraglomic targets for almitrine. The mechanisms of action of almitrine on chemoreceptor cells are discussed.

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Selected References

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  1. Almaraz L., Fidone S. Carotid sinus nerve C-fibers release catecholamines from the cat carotid body. Neurosci Lett. 1986 Jun 18;67(2):153–158. doi: 10.1016/0304-3940(86)90389-7. [DOI] [PubMed] [Google Scholar]
  2. Almaraz L., Gonzalez C., Obeso A. Effects of high potassium on the release of [3H]dopamine from the cat carotid body in vitro. J Physiol. 1986 Oct;379:293–307. doi: 10.1113/jphysiol.1986.sp016254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bisgard G. E. The response of few-fiber carotid chemoreceptor preparations to almitrine in the dog. Can J Physiol Pharmacol. 1981 Apr;59(4):396–401. doi: 10.1139/y81-063. [DOI] [PubMed] [Google Scholar]
  4. Fidone S., Gonzalez C. Catecholamine synthesis in rabbit carotid body in vitro. J Physiol. 1982 Dec;333:69–79. doi: 10.1113/jphysiol.1982.sp014439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fidone S., Gonzalez C., Yoshizaki K. Effects of low oxygen on the release of dopamine from the rabbit carotid body in vitro. J Physiol. 1982 Dec;333:93–110. doi: 10.1113/jphysiol.1982.sp014441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ganfornina M. D., López-Barneo J. Single K+ channels in membrane patches of arterial chemoreceptor cells are modulated by O2 tension. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2927–2930. doi: 10.1073/pnas.88.7.2927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lahiri S., Mokashi A., Huang W., Sherpa A. K., Di Giulio C. Stimulus interaction between CO2 and almitrine in the cat carotid chemoreceptors. J Appl Physiol (1985) 1989 Jul;67(1):232–238. doi: 10.1152/jappl.1989.67.1.232. [DOI] [PubMed] [Google Scholar]
  8. Laubie M., Schmitt H. Long-lasting hyperventilation induced by almitrine: evidence for a specific effect on carotid and thoracic chemoreceptors. Eur J Pharmacol. 1980 Jan 25;61(2):125–136. doi: 10.1016/0014-2999(80)90155-7. [DOI] [PubMed] [Google Scholar]
  9. López-Barneo J., López-López J. R., Ureña J., González C. Chemotransduction in the carotid body: K+ current modulated by PO2 in type I chemoreceptor cells. Science. 1988 Jul 29;241(4865):580–582. doi: 10.1126/science.2456613. [DOI] [PubMed] [Google Scholar]
  10. López-López J., González C., Ureña J., López-Barneo J. Low pO2 selectively inhibits K channel activity in chemoreceptor cells of the mammalian carotid body. J Gen Physiol. 1989 May;93(5):1001–1015. doi: 10.1085/jgp.93.5.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McQueen D. S., Evrard Y., Gordon B. H., Campbell D. B. Ganglioglomerular nerves influence responsiveness of cat carotid body chemoreceptors to almitrine. J Auton Nerv Syst. 1989 Jun;27(1):57–66. doi: 10.1016/0165-1838(89)90129-x. [DOI] [PubMed] [Google Scholar]
  12. Naeije R., Lejeune P., Leeman M., Melot C., Closset J. Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs. J Appl Physiol (1985) 1989 Jan;66(1):42–50. doi: 10.1152/jappl.1989.66.1.42. [DOI] [PubMed] [Google Scholar]
  13. O'Regan R. G., Majcherczyk S., Przybyszewski A. Effects of almitrine bismesylate on activities recorded from nerves supplying the carotid bifurcation in the cat. Eur J Respir Dis Suppl. 1983;126:197–202. [PubMed] [Google Scholar]
  14. Pallot D. J., Al Neamy K. W. The effects of hypoxia, hypercapnia and almitrine bismesylate on carotid body catecholamines. Eur J Respir Dis Suppl. 1983;126:203–207. [PubMed] [Google Scholar]
  15. Pequignot J. M., Tavitian E., Boudet C., Evrard Y., Claustre J., Peyrin L. Inhibitory effect of almitrine on dopaminergic activity of rat carotid body. J Appl Physiol (1985) 1987 Aug;63(2):746–751. doi: 10.1152/jappl.1987.63.2.746. [DOI] [PubMed] [Google Scholar]
  16. Ponte J., Sadler C. L. Interactions between hypoxia, acetylcholine and dopamine in the carotid body of rabbit and cat. J Physiol. 1989 Mar;410:395–410. doi: 10.1113/jphysiol.1989.sp017540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pérez-García M. T., Almaraz L., González C. Cyclic AMP modulates differentially the release of dopamine induced by hypoxia and other stimuli and increases dopamine synthesis in the rabbit carotid body. J Neurochem. 1991 Dec;57(6):1992–2000. doi: 10.1111/j.1471-4159.1991.tb06414.x. [DOI] [PubMed] [Google Scholar]
  18. Pérez-García M. T., Almaraz L., González C. Effects of different types of stimulation on cyclic AMP content in the rabbit carotid body: functional significance. J Neurochem. 1990 Oct;55(4):1287–1293. doi: 10.1111/j.1471-4159.1990.tb03137.x. [DOI] [PubMed] [Google Scholar]
  19. Rigual R., López-López J. R., Gonzalez C. Release of dopamine and chemoreceptor discharge induced by low pH and high PCO2 stimulation of the cat carotid body. J Physiol. 1991 Feb;433:519–531. doi: 10.1113/jphysiol.1991.sp018441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rocher A., Obeso A., Gonzalez C., Herreros B. Ionic mechanisms for the transduction of acidic stimuli in rabbit carotid body glomus cells. J Physiol. 1991 Feb;433:533–548. doi: 10.1113/jphysiol.1991.sp018442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rocher A., Obeso A., Herreros B., Gonzalez C. Activation of the release of dopamine in the carotid body by veratridine. Evidence for the presence of voltage-dependent Na+ channels in type I cells. Neurosci Lett. 1988 Dec 5;94(3):274–278. doi: 10.1016/0304-3940(88)90030-4. [DOI] [PubMed] [Google Scholar]
  22. Wang W. J., Cheng G. F., Yoshizaki K., Dinger B., Fidone S. The role of cyclic AMP in chemoreception in the rabbit carotid body. Brain Res. 1991 Feb 1;540(1-2):96–104. doi: 10.1016/0006-8993(91)90495-h. [DOI] [PubMed] [Google Scholar]
  23. Weiner N., Cloutier G., Bjur R., Pfeffer R. I. Modification of norepinephrine synthesis in intact tissue dy drugs and during short-term adrenergic nerve stimulation. Pharmacol Rev. 1972 Jun;24(2):203–221. [PubMed] [Google Scholar]
  24. Zigmond R. E., Schwarzschild M. A., Rittenhouse A. R. Acute regulation of tyrosine hydroxylase by nerve activity and by neurotransmitters via phosphorylation. Annu Rev Neurosci. 1989;12:415–461. doi: 10.1146/annurev.ne.12.030189.002215. [DOI] [PubMed] [Google Scholar]

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