PTH, Calcitonin, Cyclic Nucleotides and the Kidney

PARATHYROID HORMONE Cellular Basis for PTH Action Evidence for the mediation of the renal effects of parathyroid hormone (PTH) by intracellular cyclic AMP is derived from a series of observations. Recent studies have shown that cAMP originating from the kidney (ne­ phrogenous cAMP) is almost entirely accounted for by PTH-stimulated production of the nucleotide (10), with most of the net addition to the urine occurring by the end· of the accessible superficial proximal convoluted tubule (40). Virtually all of the physiologic actions of PTH on renal tubular function have been reproduced in clearance and micropuncture studies with either cAMP or dibutyryl cAMP administration (see below). These studies are not conclusive proofs. Many cyclic nucleotide analogs that resist hydrol­ ysis initially are subsequently catabolized by phosphodiesterases to 5'­ nucleotides and adenosine analogs. Adenosine in particular may have potent pharmacologic effects independent of cAMP and can alter adenylate cyclase activity.