Inhibition of the soluble guanylate cyclase from rat lung by sulfated polyanions

Soluble guanylate cyclase was partially purified from rat lung homogenates, and shown to be inhibited by the following sulfated polyanions, with the I₅₀ in μg/ml in parentheses: Polyvinyl sulfate (0.33), 40,000-dalton dextran sulfate (0.45), polyanetholesulfonate (0.63) 500,000-dalton dextran sulfate (1.8), λ-carrageenan (2.9), τ-carrageenan (6.1), κ-carrageenan (48.0), heparin (68.0). There was a good correlation between inhibitory potency and sulfate content (as total sulfur). Inhibition by heparin and the carrageenans (but not the others) was potentiated by Mn²⁺, but not Ca²⁺ or Mg²⁺, when [Mn²⁺] exceeded [GTP]. Mn²⁺-potentiation could be blocked by high Na⁺. Heparin-agarose shows promise as an affinity matrix for guanylate cyclase.