Summary
To assess the pathophysiology of the sympathetic nervous system in familial amyloidotic polyneuropathy (FAP), we used3H-bunazosin to identify and characterize the alpha1-adrenergic receptor in human aortic membranes. The binding of3H-bunazosin was rapid, readily reversible, stereospecific, and saturable. The Scatchard analysis described a single class of binding sites with a dissociation constant (KD) of 0.370±0.035nM and a maximal binding capacity (Bmax) of 11.8±1.30 fmol/mg protein in control patients. Competition analysis demonstrated the alpha1-adrenergic specificity of the3H-bunazosin binding sites in human aortic membranes. The KD and Bmax of3H-bunazosin binding in four FAP patients was 0.274±0.052 nM and 7.79±0.15 fmol/mg protein, respectively; these values did not differ significantly from those in 14 control patients. An increase in Bmax or affinity of alpha1-adrenergic receptors may not be the cause for denervation supersensitivity in FAP.
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References
Azuma T, Suzuki T, Sakoda S, Higa S, Mizuno R, Kishimoto S, Ikeda S, Yanagisawa N, Uekawa K, Takaba Y, Nakajima A (1987) α2-Adrenergic receptor in familial amyloidotic polyneuropathy. J Neurol Sci 81: 281–286
Bolton TB (1979) Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev 59: 606–718
Cambridge D, Davey MJ, Massingham R (1977) Prazosin, a selective antagonist of post synaptic α-adrenoceptors. Br J Pharmacol 59: 514–515
Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (ki) and the concentration of inhibition which cause 50 percent inhibition (IC50) of an enzymatic reaction. Biochem Pharmacol 22: 3099–3108
Colucci WS, Gimbrone MA, Alexander RW (1981) Regulation of the postsynaptic α-adrenergic receptor in rat mesenteric artery. Circ Res 48: 104–111
Glenner GG, Ignaczak TF, Page DL (1978) The inherited systemic amyloidoses and localized amyloid deposits. In: Stanbury JB, Wyngaarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease, 4th edn. McGraw Hill, New York, pp 1308–1339
Goodhardt M, Ferry N, Geynet P, Hanoune J (1982) Hepatic α1-adrenergic receptors show agonist-specific regulation by guanine nucleotides, loss of nucleotide effect after adrenalectomy. J Biol Chem 257: 11577–11583
Hata F, Kondo E, Kondo S, Kagawa K (1982) Characteristics of (3H)E-643-binding to alpha adrenoceptors. Jpn J Pharmacol 32: 181–187
Ikeda S, Hanyu N, Yanagisawa N, Hongo M, Oguchi H, Ito N (1986) Clinical and pathological studies of familial amyloid polyneuropathy (FAP), with special reference to nephropathy and cardiopathy. In: Glenner GG, Osserman EF, Benditt EP, Calkins E, Cohen AS, Zucker-Franklin D (eds) Amyloidosis. Plenum Press, New York, pp 415–428
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Michell RH (1975) Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta 415: 81–147
Sakoda S, Suzuki T, Higa S, Ueji M, Kishimoto S, Hayashi A, Yasuda N, Takaba Y, Nakajima A (1983) Genetic studies of famlial amyloid polyneurophathy in the Arao district of Japan: 1. The genealogical survey. Clin Genet 24: 334–338
Starke K, Borowski E, Endo T (1975) Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur J Pharmacol 34: 385–388
Suzuki T, Tsuge I, Higa S, Hayashi A, Yamamura Y, Takaba Y, Nakajima A (1979) Catecholamine metabolism in familial amyloid polyneuropathy. Clin Genet 16: 117–124
Suzuki T, Higa S, Tsuge I, Sakoda S, Hayashi A, Yamamura Y, Takaba Y, Nakajima A (1980) Effect of infused L-threo-3,4-dihydroxyphenylserine on adrenergic activity in patients with familial amyloid polyneuropathy. Eur J Clin Pharmacol 17: 429–435
Suzuki T, Higa S, Sakoda S, Hayashi A, Yamamura Y, Takaba Y, Nakajima A (1981) Orthostatic hypotension in familial amyloid polyneuropathy: treatment with DL-threo-3,4-dihydroxphenylserine. Neurology (NY) 31: 1323–1326
Williams LT, Mullikin D, Lefkowitz RJ (1976) Identification of α-adrenergic receptors in uterine smooth muscle membranes by3H-dihydroergocryptine binding. J Biol Chem 251: 6915–6923
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Azuma, T., Watanabe, Y., Suzuki, T. et al. The aortic alpha1-adrenergic receptor in familial amyloidotic polyneuropathy. J. Neural Transmission 73, 23–30 (1988). https://doi.org/10.1007/BF01244619
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DOI: https://doi.org/10.1007/BF01244619