Summary
The extraneuronal fate of 3H-isoprenaline was studied in the isolated rabbit iris, either non-pigmented (albino) or heavily pigmented.
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1.
On exposure to 0.1 μM 3H-isoprenaline and after inhibition of catechol O-methyltransferase (COMT), the accumulation of the amine in the pigmented iris was much more pronounced than in the albino iris (tissue/medium ratios of 6.9 and 2.2, respectively). This accumulation was only slightly reduced by inhibitors of extraneuronal uptake (30 μM phenoxybenzamine, 87 μM corticosterone).
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2.
When COMT was not inhibited, exposure to 0.1 μM 3H-isoprenaline initiated O-methylation at a constant rate (and with virtually no initial delay); steady-state rates of O-methylation were slightly lower in pigmented than in albino irides (10.7 and 14.3 pmol·g−1·min−1, respectively). However, pigmented irides retained much more O-methylated 3H-metabolite than did albino irides. As for the accumulation of unchanged amine (see above), inhibitors of extraneuronal uptake (phenoxybenzamine, corticosterone, 30 μM O-methyl-isoprenaline) caused only a slight inhibition of O-methylation.
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3.
After an initial loading of the tissue with 3H-isoprenaline, efflux curves were determined during wash-out of the tissue with amine-free solution. Compartmental analysis of such efflux curves revealed that large amounts of both 3H-isoprenaline and 3H-O-methyl-isoprenaline are retained by pigment cells, and that binding in (or to?) pigment cells is characterized by half times for efflux of more than 100 min. The longest half time for efflux from nonpigment cells (albino iris), on the other hand, was 35 min. Half times for the efflux of 3H-isoprenaline from both types of cells were not affected by the presence (during wash-out only) of 87 μM corticosterone.
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4.
It is concluded that both types of irides have a rather active O-methylating system that differs from similar systems described in other organs by being rather resistant to inhibitors of extraneuronal uptake. Pigment cells, on the other hand, have a very high binding capacity for both, amine and its metabolite, and the binding appears to be rather tight, since half times for efflux from pigment cells exceeded 2 h.
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References
Azevedo I, Osswald W (1976) Uptake, distribution and metabolism of isoprenaline in the dog saphenous vein. Naunyn-Schmiedeberg's Arch Pharmacol 295:141–147
Bausher LP, Sears M (1976) Potentiation of the effects of topical epinephrine on the pupil and intraocular pressure in the sympathetically denervated rabbit eye by a catechol-O-methyl transferase inhibitor. Invest Ophthalmol 15:854–857
Bönisch H (1978) Further studies on the extraneuronal uptake and metabolism of isoprenaline in the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 303:121–131
Bönisch H, Uhlig W, Trendelenburg U (1974) Analysis of the compartments involved in the extraneuronal storage and metabolism of isoprenaline in the perfused heart. Naunyn-Schmiedeberg's Arch Pharmacol 283:223–244
Eckert E, Henseling M, Trendelenburg U (1976) The effects of inhibitors of extraneuronal uptake on the distribution of 3H-(±)-noradrenaline in nerve-free rabbit aortic strips. Naunyn-Schmiedeberg's Arch Pharmacol 293:115–127
Farah MB, Patil PN (1979) Release and distribution of 3H-norepinephrine in nonpigmented and pigmented rabbit iris. Proc Natl Acad Sci 76:2447–2449
Fleig H, Trendelenburg U (1981) The extraneuronal sites of loss for catecholamines in guinea-pig papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol 316:14–18
Graefe K-H, Trendelenburg U (1974) The effect of hydrocortisone on the sensitivity of the isolated nictitating membrane to catecholamine. Relationship to extraneuronal uptake and metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 286:1–48
Havener W (1974) Ocular pharmacology, 3rd edition. Mosby, St. Louis, USA
Iversen LL (1965) The uptake of catechol amines at high perfusion concentrations in the rat isolated heart: A novel catechol amine uptake process. Br J Pharmacol 25:18–33
Henseling M, Eckert E, Trendelenburg U (1976) The distribution of 3H-(+)-noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes. Naunyn-Schmiedeberg's Arch Pharmacol 292:205–217
Kurahashi K, Rawlow A, Trendelenburg U (1980) A mathematical model representing the extraneuronal O-methylating system of the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 311:17–32
Major H, Sauerwein I, Graefe K-H (1978) Kinetics of the uptake and metabolism of 3H-(±)isoprenaline in the rat submaxillary gland. Naunyn-Schmiedeberg's Arch Pharmacol 305:51–63
Mack F, Bönisch H (1979) Dissociation constants and lipophilicity of catecholamines and related compounds. Naunyn-Schmiedeberg's Arch Pharmacol 310:1–9
Matheny JL, Carrier GO, Ahlquist RP (1977) Role of neuronal and extraneuronal uptake in responses of rabbit iris dilator muscle to levarterenol and phenylephrine. J Pharm Sci 66:93–95
Mintz B (1967) Gene control of mammalian pigmentary differentiation. I. Clonal origin of melanocytes. Proc Natl Acad Sci 58:344–351
Paiva MQ, Guimaraes S (1978) A comparative study of the uptake and metabolism of noradrenaline and adrenaline by the isolated saphenous vein of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 303:221–228
Patil PN (1972) Cocaine binding by the pigmented and nonpigmented iris and its relevance to the mydriatic effect. Invest Ophthalmol 11: 739–746
Patil PN (1981) Uptake and metabolism of 3H-isoprenaline in the pigmented and nonpigmented rabbit iris. Naunyn-Schmiedeberg's Arch Pharmacol 316:R54
Patil PN, Jacobowitz D (1974) Unequal accumulation of adrenergic drugs by pigmented and nonpigmented iris. Am J Ophthalmol 78: 470–477
Patil PN, Shimada K, Feller DR, Malspeis L (1974) Accumulation of (-)-14C-ephedrine by the pigmented and the nonpigmented iris. J Pharmacol. Exp Ther 188:342–352
Rawles ME (1947) Origin of pigment cells from the neural crest in the mouse embryo. Physiol Zool 20:248–266
Salazar M, Patil PN (1976) An explanation for the long duration of mydriatic effect of atropine in eye. Invest Ophthalmol 15:671–673
Salazar M, Shimada K, Patil PN (1976a) Iris pigmentation and atropine mydriasis. J Pharmacol Exp Ther 197:79–88
Salazar M, Rahwan RG, Patil PN (1976b) Binding of 14C-imipramine by pigmented and nonpigmented tissues. Eur J Pharmacol 38:233–241
Salazar M, Sokoloski TD, Patil PN (1978) Binding of dopaminergic drugs by the neuromelanin of the substantia nigra, synthetic melanins and melanin granules. Fed Proc 37:2403–2407
Seidehamel RJ, Tye A, Patil PN (1970) An analysis of ephedrine mydriasis in relationship to iris pigmentation in the guinea-pig eye in vitro. J Pharmacol Exp Ther 171:205–213
Trendelenburg U (1980) A kinetic analysis of extraneuronal uptake and metabolism of catecholamines. Rev Physiol Biochem Pharmacol 87:33–115
Uhlig W, Bönisch H, Trendelenburg U (1974) The O-methylation of extraneuronally stored isoprenaline in the perfused heart. Naunyn-Schmiedeberg's Arch Pharmacol 283:245–261
Wilkinson GN (1961) Statistical estimations in enzyme kinetics. Biochem J 80:324–332
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Supported by the Deutsche Forschungsgemeinschaft (Tr 96/12)
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Patil, P.N., Trendelenburg, U. The extraneuronal uptake and metabolism of 3H-isoprenaline in the rabbit iris. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 158–165 (1982). https://doi.org/10.1007/BF00500475
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DOI: https://doi.org/10.1007/BF00500475