The rationale of this project is that only a primary physiological (not molecular isolation and characterization of each acid-base excretory mechanism in a functionally active state will provide a logical basis for the desired biochemical isolation of those transport and regulatory (molecular) components which account for acid and alkali excretion. In order to achieve this requisite physiological isolation, it is planned in the current proposal, to reach the following general objectives: to show how exogenously added neurohormonal factors (VIP and carbachol) act to up-regulate a alkali excretion in turtle bladder; to identify factors and functional changes responsible for down-regulation of alkali excretion during systemic acidosis and for down-regulation of acid excretion during systemic alkalosis. Approaches for reaching these objectives include the following. 1. First messengers for up-regulation of alkali excretion. (1.1) To determine if vasoactive intestinal peptide (VIP) is a neuroparacrine hormonal first messenger for up-regulation of alkali excretion. (1.2) To determine if carbachol is an independent first messenger acting via the inositol-lip cascade for up-regulation of a alkali excretion. 2. Transport response to up-regulation of alkali excretion. It is planned to determine whether cAMP-induced increases in alkali excretion are due to changes in the conductance of HCO3- selective paths or Cl-selective paths. 3. Adaptation to systemic acid-base imbalance. (3.1) It is planned to determine whether adaptation of the bladder transporting mechanisms to systemic acidosis or alkalosis is associated with changes in the number or in the function of alkalinizing and acidifying cells, respectively. (3.2) It is planned to identify the extracellular factors responsible for these adaptive changes by reproducing the in vivo changes in in-vitro tissue culture.
| Youmans, S J; Brodsky, W A (1987) Vanadate inhibition of ATP-dependent H+ transport in membrane vesicles from turtle bladder epithelial cells. Biochim Biophys Acta 900:88-102 |
