Prostaglandins (PG) stimulate renin secretion through a mechanism that does not require activation of the intrarenal vascular, macula densa (MD), or beta-adrenergic receptors. In the present study the isolated perfused rat kidney was used to study the role of PG as a mediator of renin secretion when extracellular calcium was decreased and after activation of each of the intrarenal receptors. A decrease in extracellular calcium resulted in an increase in renin (from 2.1 to 4.5 ng ANG I/ml, P less than 0.01) and a decrease in PGE2 excretion (from 102 to 44 pg X min-1 X g-1, P less than 0.01). PG synthesis inhibition with indomethacin did not attenuate the increase in renin secretion. Following beta-receptor stimulation with isoproterenol, there was an increase in renin (from 2.1 to 6.6 ng ANG I/ml, P less than 0.01) not associated with changes in PGE2 excretion and not prevented by PG inhibition. When the isolated vascular receptor was stimulated by perfusing either filtering or nonfiltering kidneys below the autoregulatory range of pressure, both renin and PGE2 production were increased, and the increases were prevented by PG inhibition. The MD was activated by three methods: eliminating distal nephron fluid delivery by perfusing with hyperoncotic albumin; perfusing at 60 mmHg in the presence of papaverine; and limiting chloride transport by partially replacing chloride with nitrate in the perfusate. In each circumstance renin and PGE2 production were increased and the increase was prevented by PG inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)