Work content and satisfaction before and after a reorganisation of data entry work.

The aim of the study was to analyse the psychosocial and physical effects of a reorganisation of data entry work at a data processing unit with 153 employees. The reorganisation was planned to redistribute the repetitive work and improve health and satisfaction as well as efficiency. Methods used were questionnaires and, for a sub-group of 22 participants, interviews, diaries and video recordings. During the one-and-a-half-year study period the data processing unit was closed down and the employees transferred to units with more varied tasks. The reorganisation gave opportunities to improve working conditions. The results of this study show that important improvements were achieved. The majority of the 22 participants got less data entry work and the changes permitted a better work-load distribution. However, the work content after the reorganisation still did not provide satisfactory mental variation for most of the subjects, and the changes did not seem to affect health complaints.

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). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration-dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 microM and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 microM. The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumption in vivo the mast cell delivers histamine to restore the juxtacellular equilibrium.

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. The superfusion induces a flow of cytoplasmic K+ ions across the histamine-containing granules, resulting in an ion exchange K+ in equilibrium Hi+ ions at the histamine binding sites. The concomitant equimolar outflow of histamine and potassium is considered to be due to a functional interplay between two histamine pools, a release and a donor pool. As the result of the K+ in equilibrium Hi+ ion exchange at the histamine binding sites of the release pool, these sites become transiently occupied by K+ ions only to be immediately reoccupied by Hi+ ions from the donor pool. The observed equimolar outflows are consistent with a 1/1 molar ratio in the exchange between histamine and potassium ions. The essential role of cytoplasmic potassium in the histamine release mechanism is a new and important observation with possible implications not only as to histamine release in general (including so-called 'spontaneous' histamine release) but also as to the release of biogenic amines and other positively charged substances stored in granules in ionic linkage to the matrix.

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. Within the pH range given for the interior of the granules--5.5-6--the artificial model even stored and released CA+ and ATP- within the same molar ratio as observed for the granules. We hypothesize that the chromaffin granule matrix in its storage and release functions operates as an amphoteric ion exchanger with COO- and NH+3 groups as the binding sites.

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.

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.

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. infusion of acetylcholine in high concentration (10(-4) M). The catecholamine (CA) release, as recorded in the adrenal venous outflow, was characterized by a very steep rise to a peak (within less than 10 s), followed by a rapid decline which after 5-10 min continued as a 'steady state' secretion, still above prestimulatory level. The initial release curve satisfied the straight line equation log B = K square root (sigma ml) + log Bmax, shown previously by us to be characteristic of the cation-induced amine release from amine-charged IRC 50 (a synthetic carboxyl cation exchanger resin) and from chromaffin granules in vitro which occurred on superfusion of these materials with isotonic NaCl solution (Uvnäs & Aborg 1984a). The initial CA-release, which depending on the intensity of the stimulus amounted to between 0.1 and approximately 5% of the adrenal CA content is suggested to reflect the rapid depletion of a CA pool for immediate release composed of granules 'lined up' for secretion adjacent to the plasma cell membrane. On depolarization of this membrane the granules are assumed to become attached to it and CA release to occur as a cation exchange, between CA+ in the granule matrix and Na+ in the plasma or possibly K+ in the cytoplasm. The transition from depletion to 'steady state' phase is assumed to reflect resynthesis or other compensatory refilling of the releasable depot evoked by its depletion. Cation exchange is suggested to be a general principle in the release of biogenic amines, including transmitter amines and other co-stored charged substances, e.g. polypeptides.

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. The observations support the view that the matrices of the biogenic amine-storing granules have the properties of weak cation-exchanger materials with carboxyls as the cation-binding groups, and that the NaCl-induced release of the biogenic amines is due to cation exchange (Na+ in equilibrium Amine+). The possibility that amine release in vivo is based on cation exchange is discussed.

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. sodium ions. The proposal is made that also in vivo the release of transmitter amines is the result of cation exchange Amine+ in equilibrium Na+ ions and that the release of transmitter amines occurs as a nonexocytotic fractional release engaging multiple granules instead of exocytotic emptying of a few. Some physiological and pharmacological implications of a fractional transmitter release are discussed.

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.

In vitro studies on a two-pool stage of adrenaline and noradrenaline in granule material from bovine adrenal medulla.

Adrenal medullary granules were isolated by millipore filtration according to Poisner & Trifaró (1967) and then lysed in deionized water. In a perfusion system the influence of concentration of pH was studied on the uptake of biogenic amines (PhEA, TA, DA, NA, A, Arch and Hi) and sodium ions by lysed and by dialyzed material. The results suggest a two-pool storage of A and NA in the granules. A minor pool with cation exchanger properties binds unselectively organic (biogenic amines) and inorganic cations with a Umax of 400-500 nmol/mg granules dry-weight. This minor pool (pool 1) was fully charged at amine concentrations greater than 10 mM. A larger pool binds selectively A and NA--possibly stereospecifically L-NA and L-A--with a Umax approximately 1500 nmol/mg granules. This larger pool (pool 2) required A and NA concentrations approximately 200-300 mM for maximal filling. In pool 2 CA+ ions are assumed to be electrostatically linked to carboxyl groups, which become available as hypothetical COO----+H3N salt bridges are successively forced open by increasing CA concentrations (greater than 10-30 mM). ATP- ions become attached to the concomitantly unmasked +NH3 groups.

In vitro studies on a cation dependent catecholamine release from a two-compartment storage in bovine adrenal medullary granules.

Perfusion of adrenal medullary granules, isolated according to Poisner & Trifaró, with isotonic cation-containing solution (NaCl, KCl, LiCl) caused a concentration dependent release of CA. The course of the release indicated the existence of a two-compartment storage of CA. The minor compartment (pool 1) with a Umax of approximately 500 nmol/kg granule dry weight showed the characteristics of a cation exchanger and was assumed to be depleted on exposure to cations, e.g. sodium ions, as an ion exchange Na+ in equilibrium with CA+. The major compartment (pool 2) with a Umax of approximately 1000 nmol/mg stored both CA and ATP. It was assumed to empty via the cation exchanger pool. The total storage capacity of the two compartments approximately 1500 nmol/mg matched the in vivo storage capacity for CA (approximately 1300 nmol/mg according to Hillarp 1960).

Possible role of nerve impulse induced sodium ion flux in a proposed multivesicular fractional release of adrenaline and noradrenaline from the chromaffin cell.

Based on own observations concerning a two-compartment storage of CA in the adrenal medulla and a cation exchange dependent release of CA from perfused chromaffin granules in vitro, and encouraged by recent reports from other laboratories about the importance of sodium ions for the CA release from the adrenal gland, we propose a modification of the current quantal theory of CA secretion. Instead of secretion of quanta, each quantum corresponding to the content of one vesicle, we envisage a concomitant fractional release of CA from multiple vesicles adjacent to the chromaffin cell membrane. The CA secretion should be the result of a cation exchange across the contact area between the plasma membrane and the granule membrane during the period of depolarization caused by the nerve impulse. The size of the released quanta should be determined by the nerve impulse induced sodium ion flux and the number of such ions which reach the CA binding ionic sites in the cation exchanger pool (the release pool) of the granules.

On the cation exchanger properties of rat mast cell granules and their storage of histamine.

Mast cell granules free of a surrounding membrane were isolated from water-lysed rat peritoneal and thoracic mast cells by differential centrifugation. The granules were depleted of their histamine by suspension in 10 mM sodium phosphate buffer and the sodium-charged granules then converted into the "hydrogen form" by repeated washing in slightly acid deionized water. The cation exchanger properties of the mast cell granules were investigated by testing the applicability of the Rothmund-Kornfeld equation for cation exchangers to the binding of Na+ and Hi+ ions to granule sites. The results lend further support to the view that the mast cell granule acts as a cation exchanger with the exchanger function localized to protein carboxyls in the protein-heparin complex of the granule matrix.

The ability of ATP-free granule material from bovine adrenal medulla to bind inorganic cations and biogenic amines.

Bovine adrenal medullary granules isolated by millipore filtration were depleted of CA and ATP by dialysis. The resulting material showed an ability to bind inorganic cations and biogenic amines in a concentration-dependent manner. The similarity of the uptake curves, the identical uptake maxima and the narrow pH range (between 4-7) over which the uptake of the inorganic and organic cations took place indicated a binding of these ions to common sites. In addition, the fact that all the uptake curves fitted the Rothmund-Kornfeld equation for cation exchangers corroborated the cation exchanger properties of the dialyzed granule material. The CA binding capacity corresponded to 20-30% of the normal CA content of bovine medullary granules.

An in vitro-formed protamine-heparin complex as a model for a two-compartment store for biogenic amines.

The capacity of an in vitro-formed protamine-heparin complex (PHC) to store inorganic cations and biogenic amines was investigated. The PHC behaves like a two-compartment storage system. One compartment corresponds to the terminal free carboxyl groups of the protamine moiety and has the characteristics of a cation exchanger, with the ability to bind inorganic cations and biogenic amines in a reversible and rather unslective manner. The cations and biogenic amines therefore compete for and displace each other from the common ionic binding sites. The binding sites in the other compartment, corresponding mainly to the carboxyl groups of the heparin moiety, are only unmasked at high ionic concentrations and show a specific affinity for biogenic amines. The storage of amines in this compartment of the PHC is reversible but is dependent not only on simple ionic binding but evidently also on other attractive forces, such as dipole and hydrogen bonding.