Sodium nitroprusside inhibition of parathyroid hormone release is not mediated through cyclic GMP

Abstract

Sodium nitroprusside effected a rapid, dose-dependent increase in intracellular cGMP accumulation in freshly dispersed bovine parathyroid cells. The effect was half-maximal between 10 −4 and 3 × 10 −4M, maximal at 3 × 10 −3M nitroprusside and could be amplified (∼50%) by the addition of methylisobutylxanthine (4 × 10 −4M). The dose-response characteristics were similar to those previously described for the inhibition of cAMP accumulation and PTH release by this agent. Neither dibutyryl cGMP (10 −3M) nor 8′-bromo-cGMP (10 −3M) mimicked the inhibitory effect of nitroprusside on cAMP accumulation or PTH release. Dose-dependent stimulation of guanylate cyclase was found in a particulate preparation of parathyroid cells; activity was maximal at 10 −4M nitroprusside while higher concentrations appeared to inhibit the enzyme. Nitroprusside significantly reduced both (−)isoproterenol and guanine nucleotide-stimulated adenylate cyclase activity in the particulate preparation with maximum inhibition between 10 −3–10 −2M. cGMP concentrations as high as 10 −4M did not affect agonist-stimulated cAMP synthesis. Thus, although the kinetic and dose-response characteristics of the nitroprusside effect on cGMP suggest a linkage to its previously described effects on cAMP and PTH secretion, no direct evidence was found to indicate a causal relationship between the two. Rather it would appear that the effects on the adenylate and guanylate cyclase enzymes occur in parallel, possibly the result of some common primary perturbation of cellular physiology.