Metabolites of arachidonic acid like prostaglandins have an established role in the pathogenesis of gallstone formation and cholecystitis, but any contribution by leukotrienes is less clear. Leukotrienes might contribute to the disease process by contracting the inflamed and (or) obstructed gallbladder, resulting in further inflammatory damage and biliary pain. To better define the role of leukotrienes, we assessed their effects on gallbladder contractility in vitro. Both leukotriene C4 (LTC4) and D4 (LTD4) had a concentration-dependent excitatory effect on guinea-pig gallbladder smooth muscle. The LTD4-receptor antagonist MK-571 (1 microM) competitively depressed the contractile response, to both LTD4 and LTC4. The source of calcium was defined using ryanodine to deplete intracellular calcium stores and nifedinine to block extracellular entry. Ryanodine (10 microM) antagonized gallbladder contraction at low concentrations of LTD4 (10(-10) and 10(-9) M). Nifedipine (1 microM) had a greater inhibitory effect on the contractile response at high concentrations of LTD4 (10(-8)-10(-6) M). LTD4-induced contractions were unaffected in tissues pretreated with the neural blocker tetrodotoxin or the muscarinic antagonist atropine. Thus, leukotrienes act directly on the gallbladder smooth muscle, causing contraction at concentrations found in models of cholecystitis, suggesting that these inflammatory mediators contribute to the symptoms and morbidity associated with gallbladder disease.

Ecological succession theory can be used in land-use planning to develop self-maintaining systems that meet conservation needs. This paper presents a management succession model and outlines methods that can be applied to regional land-use, rangeland, and agro-ecosystem, management. Traditionally, succession has been viewed as a repeatable and deterministic change in an ecosystem. Unlike the traditional view, the management succession model suggests that the successional process can be regulated to develop management designed communities. The model is based on current succession theory and consists of five steps; designed disturbance, selective colonization, inhibitory persistence, removal, and regeneration. Through the steps of the model, community interactions, life-history characteristics, and those abiotic factors that are to some extent controllable, are manipulated. The objective in manipulating these factors is to regulate successional sequences and rates of species replacement.To implement these steps a management practice, such as burning, can be used as a designed disturbance. The timing, intensity, and extent, of burning are regulated to insure that ‘selected colonizers’ become established. The design of the disturbance, and the selection of species and proportions of colonizers, is based upon the type of community structure that is wanted. Often a stable, persisting community is the goal. How long a community persists can be controlled by planned removal, which deliberately interrupts a successional sequence. The removal process can, in itself, be considered a type of disturbance, and can be used to regulate subsequent successional sequences and rates of replacement. In some instances a regenerating community is the goal, and management efforts can be adjusted to prevent successional sequences from occurring.

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