ABSTRACT
BACKGROUND: Beta(2)-adrenoceptor agonists are effective bronchodilators. In vitro studies demonstrated long-lasting airway smooth muscle relaxation by salmeterol after washout, the quick disappearance of this effect in presence of antagonists and its recovery after antagonist removal. Current explanations invoke salmeterol accumulation in the membrane ('diffusion microkinetic' model) or the existence of salmeterol-binding 'exosites'. An alternative model based on 'rebinding' of a dissociated ligand to the receptor molecules also produces an apparent decrease in the ligand's dissociation rate in the absence of competing ligands. PURPOSE AND APPROACH: Computer-assisted simulations were performed to follow the receptor-occupation by a salmeterol-like ligand and a competing ligand as a function of time. The aptness of the models to describe the above in vitro findings was evaluated. KEY RESULTS: The 'diffusion microkinetic' model is sufficient to explain a long-lasting beta(2)-adrenoceptor stimulation and reassertion as long as the membrane harbors a high concentration of the agonist. At lower concentration, 'rebinding' and, in second place, 'exosite' binding are likely to become operational. CONCLUSIONS AND IMPLICATIONS: The 'rebinding' and 'exosite' binding mechanisms take place at a sub-cellular/molecular scale. Pending their demonstration by experiments on appropriate, simple models such as intact cells or membranes thereof, these mechanisms remain hypothetical in the case of salmeterol. Airway smooth muscle contraction could also be governed by additional mechanisms that are particular to this macroscopic approach.
Subject(s)
Adrenergic beta-2 Receptor Agonists , Adrenergic beta-Agonists/metabolism , Albuterol/analogs & derivatives , Bronchodilator Agents/metabolism , Models, Biological , Receptors, Adrenergic, beta-2/metabolism , Adrenergic beta-Agonists/chemistry , Albuterol/chemistry , Albuterol/metabolism , Bronchodilator Agents/chemistry , Cell Line , Humans , Protein Binding/physiology , Receptor, Cannabinoid, CB1/metabolism , Salmeterol XinafoateABSTRACT
We investigated the responses to insect prey (dead houseflies) in 24 "derivative groups" of workers of the ant Formica polyctena created by taking sets of 25 workers out of nine larger "initial groups" kept in laboratory without queens and brood during the preceding five months. In the derivative groups the ants ceased to retrieve flies to their nests after a period ranging from few days to several weeks. The duration of that period did not depend on the present size of the derivative group (decreasing as a result of worker mortality), but was positively correlated with the estimated size of the initial group of the tested ants. The readiness to display venom spraying was higher in smaller derivative groups. These data demonstrate that responses of F. polyctena to insect prey are strongly influenced both by the present and the past size of their group.
Subject(s)
Ants/physiology , Feeding Behavior/physiology , Predatory Behavior/physiology , Social Behavior , Animals , Behavior, Animal/physiologyABSTRACT
Fifty six diabetic patients aged 25-74 were under ophthalmological control in the period 1984-87. The mean time of duration of diabetes amounted 14 years. In 29 persons diabetes was insulinodependent and in the remaining insulino-independent. In 11 eyes the fundus exhibited diabetic changes with characteristics of angiopathy, in 43 eyes--of exudative retinopathy and in 58 eyes of proliferative retinopathy. Photocoagulation with a xenon-arc lamp of the diabetic changes was performed in all the patients. In dependence of the extent of the changes one used either a focused or a panretinal photocoagulation. In the majority of cases one could stop the progress of the diabetic changes on the fundus and preserve a fair visual acuity.
