Demonstration and Quantitation of Pharmacological Inhibition of Pulmonary Uptake of N-lsopropyl-¹²³l-p-lodoamphetamine by Propranolol

The first-pass pulmonary extraction values of N-lsopropyl-¹²³l-p-lodoamphetamine (¹²³I-IMP) in pretreated dogs decreases from 90 to 62% as the amount of propranolol increases from 0 to 20 mg. The first-pass pulmonary extraction values of ¹²³I-IMP in dogs with a simultaneous bolus injection of propranolol decreases from 90 to 62% as the amount of propranolol increases from 0 to 10 mg. The pulmonary extraction of ¹²³I-IMP with a simultaneous bolus injection of ketamine and ¹²³I-IMP decreases from 90 to 64% as the ketamine dose increases from 0 to 100 mg. These results suggest that the pulmonary uptake of ¹²³I-IMP may be at least partially mediated by receptors. They also indicate that endothelial metabolic cell function may be a useful index of early lung pathology. Furthermore, studies of the degree of lung uptake may be a sensitive index of pathologic states in which alterations of amine binding sites have occurred.

Zusammenfassung

Die First-pass-Lungenextraktionswerte von n-Isopropyl-¹²³J-p-Jodamphetamin (¹²³J-IMP) fallen bei unbehandelten Hunden von 90 auf 62%, wenn die Propranololmenge von 0 auf 20 mg erhöht wird. Die First-pass-Lungenextraktionswerte von ¹²³J-IMP bei Hunden fallen nach einer gleichzeitigen Bolusinjektion von Propranolol von 90 auf 62%, wenn die Propranololmenge von 0 auf 10 mg erhöht wird. Die Lungenextraktion von ¹²³JIMP fällt nach einer gleichzeitigen Bolusinjektion von Ketamin und ¹²³JIMP von 90 auf 64%, wenn die Ketaminmenge von 0 auf 100 mg erhöht wird. Diese Ergebnisse legen nahe, daß die pulmonale Aufnahme von ¹²³J-IMP zumindest teilweise über Rezeptoren erfolgt. Sie weisen auch darauf hin, daß die Stoffwechselfunktion der endothelialen Zellen ein nützlicher Index für frühe Lungenerkrankungen sein könnte. Schließlich könnten Untersuchungen der Lungenspeicherung ein empfindlicher Index für Krankheitszustände sein, bei denen Veränderungen der Bindungsstellen für Amine eingetreten sind.

• REFERENCES

• 1 Akber S F. Ketamine influence on the first pass pulmonary extraction of N-isopropyl-I-123-p-Iodoamphetamine using indicator dilution technique. Proc, 14th Internation Conf on Medicine and Biological Engineering and Computing 1985; 23 (Suppl, Part 2): 1377-8.
• 2 Akber S F. On the theory of the measurement of the first pass pulmonary extraction using the indicator dilution technique. Nucl Med 1987; 26: 20-7.
• 3 Akber S F. A noninvasive assessment of pharmacological interaction of amines in the lung. Nucl Med Commun 1987; 08: 889-93.
• 4 Anderson M W, Orton T C, Pickett R D, Eling T E. Accumulation of amines in the isolated perfused rabbit lung. J Pharmacol Exp Ther 1974; 189: 456-66.
• 5 Black J W, Duncan W A M, Shanks R G. Comparison of some properties of pronethalol and propranolol. Br J Pharmacol 1965; 25: 577-91.
• 6 Cohen M L, Chan S L, Trevor A J. In vitro inhibition of rat brain norepinephrine uptake and acetylcholinesterase by ketamine. Fed Proc 1973; 32: 682.
• 7 Dollery C T, Junod P J. Concentration of (+)-propranolol in isolated perfused lungs of rat. Br J Pharmacol 1976; 57: 67-71.
• 8 Drew G, Nicholls P J. Uptake of amphetamine by guinea pig lung in vitro. J Pharm Pharmacol 1978; 30 (Suppl. 01) 55.
• 9 Gallagher B M, Christman D, Fowler J. et al. Radioisotope scintigraphy for the study of dynamics of amine regulation in the human lung. Chest 1977; 71 (Suppl. 02) 282-4.
• 10 Gcddes D B, Nesbitt K, Traill T. et al. First pass uptake of C-14-propranolol by the lung. Thorax 1979; 34: 810-3.
• 11 Gillis C N, Cronau L H, Mandel L, Hammond G L. Indicator dilution measurement of 5-hydroxytryptamine clearance by human lung. J Appl Physiol Resp Env Exer Physiol 1979; 46: 1178-83.
• 12 Gillis C N, Pitt B R. The fate of circulating amines within the pulmonary circulation. Ann Rev Physiol 1982; 44: 269-81.
• 13 Hayes A, Cooper R G. Studies on the absorption, distribution and excretion of propranolol in rat, dog and monkey. J Pharmacol Exp Ther 1971; 176: 302-11.
• 14 Hemsworth B A, Street J A. Characteristic of (+)-(C-14)-oxyprenolol and (+)-(C-14)-propranolol incorporation by rat lung slices. Br J Pharmacol 1981; 73: 119-25.
• 15 Lin T H, Mar B M, Wu J L. et al. Brain localization and octonol/water PC-pH profiles of radioiodinated amines: evidence against “pH shift”. J Nucl Med 1984; 25: 111.
• 16 Lu J L, Lin T H, Bruggman T C. Metabolism of I-125-M-123 in the rat. Progress Report, Medi + Physics, Inc. April 27, 1981
• 17 Medi + Physics: Personal communication.
• 18 Orton T C, Anderson M W, Pickett R D, Eling T E, Fouts J R. Xenobiotic accumulation and metabolism by isolated perfused rabbit lungs. J Pharmacol Exp Ther 1973; 186: 482-97.
• 19 Pang J A, Blackburn J P, Butland R J A, Corrin B, Williams T R, Geddes D M. Propranolol uptake by dog lung: effect of pulmonary artery occlusion and shock lung. J Appl Physiol 1982; 49: 393-401.
• 20 Rahimian J, Glass E C, Touya J J, Akber S F, Graham S L, Bennett L R. Measurement of metabolic extraction of tracers in the lung using multiple indicator dilution technique. J Nucl Med 1984; 25: 31-7.
• 21 Schneck D W, Pritchard J F, Hayes A H. et al. Studies on the uptake and binding of propranolol by rat tissues. J Pharmacol Exp Ther 1977; 203: 621-9.
• 22 Slosman D O, Brill A B, Polla B S, Alderson P O. Evaluation of (Iodine-125) N,N;N’-trimethyl-N’-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine lung uptake using an isolated-perfused lung model. J Nucl Med 1987; 28: 203-8.
• 23 Som P, Oster Z H, Yamamoto K. et al. Some factors affecting the cerebral and extracerebral accumulation of N-isopropyl-I-123-piodoamphetamine (IAMP). Int J Nucl Med Biol 1985; 12: 185-96.
• 24 Steinberg H, Bassett D J P, Fisher A B. Depression of pulmonary 5-hydroxy-tryptamine uptake by metabolic inhibitors. Am J Physiol 1975; 228: 1298-303.
• 25 Syrota A, Pascal O, Crouzel M. et al. Pulmonary extraction of C-11 chlorpromazine, measured by residue detection in man. J Nucl Med 1981; 22: 145-8.
• 26 Touya J, Akber S F, Rahimian J, Bennett L R. Metabolic lung scanning with N-isopropyl-I-123-iodoamphetamine. In: Reynaud Third World Congr of Nucl Med and Biol. Oxford: Pergamon; 1982: 2554-7.
• 27 Touya J J, Rahimian J, Grubbs D E, Corbus H F, Bennett L R. A noninvasive procedure for in vivo assay of a lung amine endothelial receptor. J Nucl Med 1985; 26: 1302-7.
• 28 Winchcll H S, Horst W D, Braun L, Oldendorf W H, Hattner R, Parker H. N-isopropyl-I-123-p-iodoamphetamine: Single pass brain uptake and wash out; binding to brain synaptosomes; and localization in dog and monkey brain. J Nucl Med 1980; 21: 947-52.