Summary
Peripheral-type benzodiazepine binding sites on intact platelets from untreated chronic insomniac patients and those chronically treated with benzodiazepine hypnotics were investigated to evaluate their putative involvement in sleep pathology and the influence of treatment. There were 34 elderly subjects in the study, 14 controls (80.7 years) and 20 insomniac patients, of whom 7 were untreated (61.1 years) and 13 were treated (84.4 years). There was an equivalent number of peripheral-type benzodiazepine 3H-PK 11195 binding sites on platelets from untreated (7.61 pmol/mg protein) and treated insomniacs (6.39 pmol/mg protein) and on platelets from the controls (6.21 pmol/mg protein). However, there was a twofold reduction in the affinity of these sites in untreated (Kd=8.02 nM) and treated (Kd=7.40 nM) insomniacs compared to controls (3.79 nM). This difference raises the possibility that peripheral-type benzodiazepine sites are involved in abnormal sleep.
References
Braestrup C, Squires RF (1977) Specific benzodiazepine receptors in rat brain characterized by high affinity 3H diazepam binding. Proc Natl Acad Sci USA 74: 3805–3809
Möhler H, Okada T (1978) Biochemical identification of the site of action of benzodiazepine in human brain by 3H diazepam binding. Life Sci 22: 985–996
Charbonneau P, Syrota A, Crouzel C, Valois JM Prenant C, Crouzel M (1986) Peripheral benzodiazepine receptors in the living heart characterized by positron emission tomography. Circulation 73: 476–483
Anholt RRH, Pedersen PL, De Souza EB, Snyder SH (1986) The peripheral-type benzodiazepine receptors. J Biol Chem 261: 576–583
De Souza EB, Anholt RRH, Murphy KMM, Snyder SH, Kuhar MJ (1985) Peripheral type benzodiazepine receptors in endocrine organs: Autoradiographic localization in rat pituitary, adrenal and testis. Endocrinology 116: 567–573
Pazos A, Cymerman U, Probst A, Palacios JM (1986) Peripheral benzodiazepine binding sites in human brain and kidney: Autoradiographic studies. Neurosci Lett 66: 147–152
Marangos PJ, Patel J, Boulenger JP, Clark-Rosenberg R (1982) Characterisation of peripheral type benzodiazepine binding sites in brain using 3H RO 5-4864. Molec Pharmacol 22: 26–32
Guilleminault C, Silvestri R (1982) Aging, drug and sleep. Neurobiol Aging 3: 379–386
Hammond E (1966) Some preliminary findings on physical compaints from a prospective study of 1,064,004 men and women. Am J Publ Health 54: 11–23
Levi F, Benavides J, Touitou Y et al. (1986) Circadian rhythm in peripheral type benzodiazepine binding sites in human platelets. Biochem Pharmacol 35: 2623–2625
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagents. J Biol Chem 193: 265–275
Johnson MD, Wang JKT, Morgan JI, Spector S (1986) Downregulation of 3H RO-5 4864 binding sites after exposure to peripheral type benzodiazepine in vitro. J Pharmacol Exp Ther 238: 855–859
Benavides J, Quarteronet D, Plouin PF, Imbault F, Phan T, Uzan A, Renault C, Dubroeucq MC, Gueremy C, Le Fur G (1984) Characterization of peripheral benzodiazepine binding sites in human and rats platelets by using 3H PK 11195. Studies in hypertensive patients. Biochem Pharmacol 33: 2467–2472
Gavish M, Weizman A, Karp L, Tyano S, Tanne Z (1986) Decreased peripheral benzodiazepine binding sites in platelets of neuroleptic-treated schizophrenics. Eur J Pharmacol 121: 275–279
Verma A, Nye JS, Snyder SH (1987) Porphyrins are endogenous ligands for the mitochondrial (peripheral type) benzodiazepine receptors. Proc Natl Acad Sci USA 84: 2256–2260
Beaumont K, Cheung AK, Geller ML, Fanestil DD (1983) Inhibitors of peripheral-type benzodiazepine receptors in human urine and ultra filtrates. Lif Sci 33: 1375–1384
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gilbert, J.C., Valtier, D., Huguet, R. et al. Reduced affinity of peripheral benzodiazepine binding sites in elderly insomniac patients. Eur J Clin Pharmacol 34, 303–306 (1988). https://doi.org/10.1007/BF00540960
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00540960