The molecular mechanism of nondegranulative release of biogenic amines.

According to current teaching biogenic amines are released by exocytosis, i.e. by evacuation of amine storing vesicles or granules into the extracellular space.

Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells.

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the 'state of equilibrium' at the cell surface caused by the superfusion (Uvnäs et al. 1989).

Urinary bladder and urethral responses to pelvic and hypogastric nerve stimulation and their relation to vasoactive intestinal polypeptide in the anaesthetized dog.

The effects on the urinary bladder and urethra of pelvic and hypogastric nerve stimulation and their relation to vasoactive intestinal polypeptides (VIP) were investigated in the anaesthetized dog. Both pelvic and hypogastric nerve stimulation elicited a twofold increase in urinary bladder blood flow and a clear-cut increase in bladder venous effluent VIP concentration. Hypogastric nerve stimulation induced an initial, partly alpha-adrenergic and partly non-adrenergic, non-cholinergic, contraction of the urinary bladder followed by a relaxation.

Intracellular ion exchange between cytoplasmic potassium and granule histamine, an integrated link in the histamine release machinery of mast cells.

Rat peritoneal mast cells isolated by gradient centrifugation in Percoll were placed between two membrane filters in a Sartorius filter apparatus and superfused with isotonic balanced salt solutions or with deionized isotonic sucrose. Histamine was released according to ion exchange kinetics. Our explanation of the observed phenomena is as follows.

Occurrence of an insulin-like peptide in extracts of human nervous tissue.

Peripheral nerves of the cat such as the vagal and the sciatic nerves have been shown to contain a peptide with insulin-like properties. The aim of the present study was to investigate whether insulin-like immunoreactivity (ILI) can be demonstrated in human nervous tissue collected from autopsy material. Biopsies were taken in connection with autopsy from various peripheral nerves and their content of ILI was investigated.

Catecholamines (CA) and adenosine triphosphate (ATP) are separately stored in bovine adrenal medulla, both in ionic linkage to granule sites, and not as a non-diffusible CA-ATP-protein complex.

On superfusion of chromaffin granules from bovine adrenals with isotonic sodium and potassium salts, catecholamines and ATP were released in parallel and both in accordance with ion exchange kinetics. An artificial model was prepared by mixing a cationic (IRC-50) and an anionic (IR-4B) ion exchanger with COO- and NH+3 groups, respectively, as binding sites. This mixed ion exchanger showed in its storage and release of CA+ and ATP- striking similarities to the chromaffin granules.

Do superfused mast cells release histamine by endogenous cation exchange with potassium ions?

Isolated rat peritoneal mast cells released histamine on superfusion with isotonic salt solutions or isotonic deionized sucrose. The histamine release followed the kinetics of cation exchange characteristic of the release from similarly superfused isolated mast cell granules and histamine charged carboxylic resin IRC-50. The histamine release was accompanied by an efflux of potassium and ascribed to an endogenous cation exchange K+ in equilibrium with Hi+ occurring on the passage of outflowing potassium ions over histamine storing granules.

Release of an insulin-like peptide from perfused extirpated cat legs in response to electrical stimulation of the sciatic and brachial nerves and to administration of ACh, bombesin, oxytocin and glibenclamide.

The vascular system of extirpated cat legs was perfused with Tyrode's solution and insulin-like immunoreactivity (ILI) levels were determined in the perfusate with radioimmunoassay. During unstimulated conditions perfusate levels of ILI were almost undetectable. However, in response to electrical stimulation of the sciatic or brachial nerves (within a wide range of stimuli 5-40 V, 2-20 Hz and 0.

Cation exchanger properties of isolated rat peritoneal mast cell granules.

The synthetic carboxylic cation exchanger resin Amberlite IRC-50 was charged with histamine by suspension in histamine-containing solution with admixture of [14C]histamine. Mast cell granules were isolated from mast cells suspended in isotonic sucrose. The release of histamine induced from the two materials by superfusion with isotonic NaCl and KCL solutions showed identical kinetics, in accordance with the view that the release of histamine is due to a cation exchange: Na+ (K+) in equilibrium Hi+ at carboxyl groups in the granule heparin-protein complex.

Cation-induced histamine release from a synthetic weak (carboxylic) cation exchanger resin (IRC-50) and from isolated mast cell granules show identical kinetics.

Comparative studies between synthetic weak cation exchanger resins and rat mast cell granules have shown that the cation-induced release of histamine from both materials follows the kinetics characteristic of cation exchange. Since also cation-induced release of amines from chromaffin granules in vitro and chromaffin cells in vivo, as also nerve granules of peripheral and central neurons, run according to cation exchange kinetics, cation exchange might be a general principle in the storage and release of biogenic amines.

The kinetics of adrenal catecholamine secretion elicited by splanchnic nerve stimulation or by Ach is consistent with non-exocytotic, multivesicular release on cation exchange basis.

In eight anaesthetized cats, one dog and one pig the left adrenal was activated during a 5-15-min period by splanchnic nerve stimulation (10-30 V, 0.2-2 ms) at supramaximal frequencies (10-50 Hz) or by i.a.

Cation exchange--a common mechanism in the storage and release of biogenic amines stored in granules (vesicles)? II. 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.

Superfusion of phenylethylamine-, noradrenaline- or histamine-charged weak (carboxyl) cation-exchangers (IRC-50 and Duolite CS-100) with isotonic NaCl caused a release of the amines. Similarly, bovine chromaffin granules and nerve granule preparations from bovine splenic nerve, rat vas deferens and rat corpus striatum released their amine(s) upon superfusion with the same solution. The courses of release from the synthetic and biogenic materials showed very similar characteristics and fitted the same exchange equations.

Cation exchange--a common mechanism in the storage and release of biogenic amines stored in granules (vesicles)? III. A possible role of sodium ions in non-exocytotic fractional release of neurotransmitters.

The matrices of the amine storing granules in mast cells, chromaffin cells and noradrenergic nerves show properties reminiscent of cation exchanger materials. In vitro, the amines are released from their granule storage sites on exposure of the granules to cations, e.g.

Cation exchange--a common mechanism in the storage and release of biogenic amines stored in granules (vesicles)? I. Comparative studies on the uptake of sodium and biogenic amines by the weak cation (carboxyl) exchangers Amberlite IRC-50 and Sephadex C-50 and by biogenic (granule-enriched) materials in vitro.

Studies on the uptake and storage of sodium and biogenic amines (phenylethylamine, noradrenaline, histamine) by two weak cation-exchangers, IRC-50 and Sephadex C-50, and by biogenic granule-enriched preparations demonstrated that the synthetic and biogenic materials had several common characteristics. They showed similar concentration- and pH-dependence and fitted the same cation-exchange and receptor-binding equations. The observations were taken to support the view that the matrices of amine-storing granules have the properties of weak cation-exchangers, with carboxyls as the cation-binding groups.

Occurrence of an insulin-like peptide in extracts of peripheral nerves of th cat and in extracts of human vagal nerves.

Biopsies from various peripheral nerves were collected from living cats. The biopsies were extracted with acid ethanol and the insulin-like immunoreactivity (ILI) content of the extracts determined with radioimmunoassay. The vagal, sciatic and radial nerves contained on the average 90, 3 and 28 ng of ILI per gram nerve tissue (wet weight), respectively.

The distribution of somatomedins in the nervous system of the cat and their release following neural stimulation.

Recent evidence suggests a regulatory role in the nervous system for somatomedins. The present study, using a somatomedin radioreceptorassay which primarily detects insulin-like growth factors 1 and 2, shows that somatomedins are widely distributed throughout the nervous system of the cat. Whilst somatomedins were present in all CNS regions, the highest concentration occurred in the hypothalamus followed by cerebral cortex.