The molecular mechanism of nondegranulative release of biogenic amines

• Autorzy: Uvnas B.
• Języki publikacji: EN

Abstrakty

EN

According to current teaching biogenic amines are released by exocytos- is, i. e. by evacuation of amine storing vesicles or granules into the extracellular space. The release of transmitter amines is quantal, i. e. occurs in packs of transmitter molecules. These packs are assumed to be identical with vesicle contents, in other words, the smallest releasable quantum equals the amine content of one vesicle. However, there are experimental observations which do not fit in with this version of an exocytotic release theory. Observed quantitative discrepancies could be explained if the release mechanism allowed a fractional release of transmitter amine from several vesicles instead of the total evacuation of a few. The lack of adequate knowledge about the mechanisms of storage of biogenic amines within the vesicles has up til now rendered it difficult to envisage the machinery behind a fractional release of the amine content of a vesicle. In extensive in-vitro studies we have found that the matrices of amine storing granules (i. e. from mast cells, chromaffin cells and nerve terminals) show the properties of weak cation exchanger materials, carboxyl groups serving as amine binding ionic sites. When exposed to cations like sodium and potassium ions, the amines are released from their storage sites according to kinetics characteristic of weak cation exchangers. In vivo, amine release from cat adrenals on splanchnic nerve stimulation also occurs according to ion echange kinetics. Histamine release from mast cells is considered to occur as the result of degranulation, i. e. the expulsion of histamine storing granules to the extracellular space, a typical example of exocytosis. The granules are assumed to loose their histamine by ion exchange, Na⁺ Hi⁺, on exposure to the sodium-rich extracellular medium. However, recent observations on histamine release from superfused mast cells suggest that the release of histamine, although caused by ion exchange, is due to intracellular ion exchange at granule sites between cytoplasmic potassium and activated mast cells as the consequence of intracellular potassium ion flux across the histamine carrying granules, degranulation and extracellular histamine release from expelled granules occurring only as the result of more extensive activation. The possibility of potassium ions being involved also in an ion exchange process behind the release of other biogenic amines e. g. at nerve terminals will be proposed. The amine release will still be quantal but the size of the released quanta will not depend on the total amine content of a vesicle but on the size of the fractions thereof being released, thereby explaining many of the quantitative discrepancies attached to the current exocytotic release theory. A fractional release theory may have interesting consequences for our thinking as to the physiology and pharmacology of processes involving storage and release of biogenic amines.

Słowa kluczowe

EN

ion exchange; biogenic amine; chromaffin cell; mast cell; histamine; catecholamine; molecular mechanism

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 1991
• Tom: 42
• Numer: 2
• Opis fizyczny: p.211-219,fig.,ref.

Twórcy

autor

Uvnas B.

• Department of Pharmacology, Karolinska Institutet, Box 60400, S-104 01 Stockholm, Sweden

Bibliografia

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• 5. Uvnäs В, Ȧborg C-H. Cation exchange - a common mechanism in the storage and release of biogenic amines stored in granules (vesicles?). Comparative studies on sodium-induced release of biogenic amines from the synthetic weak cation-exchangers Amberlite IRC-50 and Duolite CS-100 and from biogenic (granule-enriched) materials. Acta Physiol Scand 1984: 120: 87-97.
• 6. Uvnäs В, Ȧborg C-H. Catecholamines (CA) and adenosine triphosphate (ATP) are separately stored in bovine adrenal medulla, both in ionic linkage to granule sites, and not as a nondiffusable CA-ATP-protein complex. Acta Physiol Scand 1988; 132: 297-312.
• 7. Uvnäs В, Ȧborg C-H, Goiny M. The kinetics of adrenal catecholamine secretion elicited by splanchnic nerve stimulation or by acetylcholine is consistent with non- exocytotic, multivesicular release on cation exchange basis. Acta Physiol Scand 1985; 123: 249-259.
• 8. Uvnäs В, Ȧborg C-H, Lyssarides L, Thyberg J. Cation exchanger properties of isolated rat peritoneal mast cell granules. Acta Physiol Scand 1985; 125: 25-31.
• 9. Uvnäs В, Ȧborg C-H, Lyssarides L, Thyberg J, Danielsson L-G. Rat mast cells superfused with isotonic solutions release histamine, probably via intracellular cation exchange K⁺ Hi⁺ ions. Acta Physiol Scand 1986; 128: 657-658.
• 10. Uvnäs В, Ȧborg C-H, Lyssarides L, Danielsson L-G. Intracellular ion between cytoplasmic potassium and granule histamine, an integrated link in the histamine release machinery of mast cells. Acta Physiol Scand 1989; 136: 309-320.
• 11. Uvnäs В, Ȧborg C-H, Lyssarides L, Danielsson L-G. Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells. Acta Physiol Scand 1991; 142: 173-180.