Abstract
A specific and sensitive radioimmunoassay (RIA) for the histamine H2-antagonist, tiotidine, has been developed. The assay is based upon competition of tiotidine with [3H]-tiotidine for antibody (Ab) obtained from immunized rabbits. The immunogen used was a glutaraldehyde coupled conjugate of the tiotidine derivative (ICI 147,655) and bovine serum albumin (BSA). Displacement of [3H]-tiotidine by unlabeled tiotidine was competitive over a concentration range of 10–1000 fmol. The Ab was 100-fold less sensitive to the pharmacologically inactive metabolite of tiotidine (ICI 129,585) and did not cross-react with histamine, cimetidine or phenylguanidine. In dogs given an i.v dose of tiotidine, plasma levels of the antagonist, as measured by the RIA, were correlated with inhibition of histamine-induced gastric acid secretion. Tiotidine (0.3 or 0.6 μmol kg−1) caused a dose-dependent and transient decrease in acid secretion at plasma concentrations of 10−6 to 10−8 M. Other potential analytical and research uses of H2-antagonist radioimmunoassays are discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
J.W. Black, W.A.M. Duncan, G.J. Durant, C.R. Ganellin andM.E. Parsons,Definition and antagonism of histamine H 2 -receptors, Nature236, 385–390 (1972).
R.E. Pounder,Has cimetidine revolutionised the medical treatment of peptic ulceration, J. hum. Nutr.33, 367–70 (1979).
T.O. Yellin, S.H. Buck, D.J. Gilman, D.F. Jones andJ.M. Wardleworth,ICI 125,211: a new gastric antisecretory agent acting on histamine H 2 -receptors, Life Sci.25, 2001–2009 (1979).
N.E. Larsen, P. Hesselfeldt, S.J. Rune andE.F. Hvidberg,Cimetidine assay in human plasma by liquid chromatography, J. Chromat.163, 57–63 (1979).
K. Monson, R.K. Simon andJ.O. Malbica,Quantitative high-performance liquid chromatography determination of ICI 125,211 in plasma, J. analyt. Toxic4, 244–279 (1980).
R.M. Lee andP.M. Osborne,High-pressure liquid chromatography determination of dimetidine sulphoxide in human blood and urine, J. Chromat.146, 354–360 (1978).
D.A. Chiarmonte andJ.J. Schentag,A specific and sensitive high pressure liquid chromatographic procedure for dimetidine and creatinine, Ther. Drug Monitoring1, 545–554 (1979).
W.N. Jenner, L.E. Martin, B.A. Willoughby andI. Fellows,The development of a radioimmunoassay for ranitidine in biological fluids, Life Sci.28, 1323–1329 (1981).
B.F. Erlanger,Principles and methods for the preparation of drug protein conjugates for immunological studies, Pharmac. Rev.25, 271–280 (1973).
K.L. Melmon, Y. Weinstein, T.C. Poon, H.R. Bourne, G.M. Shearer, P. Coffino andP.A. Insel, Receptors for low-molecular-weight hormones on lymphocytes. InImmunopharmacology pp. 331–356 (EdsJ.W. Hadden, R.G. Coffey andF. Spreafico). Plenum, New York 1977.
O.H. Lowry, N.J. Roseborough, A.L. Farr andR.J. Randall,Protein measurements with the folin phenol reagent, J. biol. Chem.193, 265–275 (1951).
Y.P. Butler, Immunoassay of drugs and the biological use of antidrug antibodies. InImmunopharmacology, pp. 315–330 (EdsJ.W. Hadden, R.G. Coffey andF. Spreafico). Plenum, New York 1977.
J.S. Garvey, N.E. Cremer andD.H. Sussdorf, Bleeding of animals. InMethods in Immunology, pp. 20–38. W. A. Benjamin, Reading 1977.
D. Rodbard, W. Bridson andP.L. Rayford,Rapid calculation of radioimmunoassay results, J. Lab. clin. Med.74, 770–776 (1969).
R.C. Rodgers,RIA Theory for Health Care Professionals, pp. 31–51. Hewlett Packard, USA.
Y. Weinstein, K.L. Melmon, H.R. Bourne andM. Sela,Specific leukocyte receptors for small endogeneous hormones, J. clin. Invest.52, 1349–1361 (1973).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dobson, P., Yellin, T.O. A radioimmunoassay for the histamine H2-antagonist, tiotidine. Agents and Actions 15, 162–166 (1984). https://doi.org/10.1007/BF01972343
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01972343