Chloroquine inhibits arginine vasopressin production in isolated rat innermedullary segments induced cAMP collecting duct

Previous studies showed that acute chloroquine administration increases pla sma arginine vasopressin (AVP) concentration in the rat without influencing urine flow rate. The present study was designed to investigate whether chl oroquine inhibits the AVP-induced cAMP production that mediates the antidiu retic effects of vasopressin. Single inner medullary collecting duct (IMCD) segments were pre-incubated at 35 degrees C for 10 min followed by 4 min a t 37 degrees C with combinations of AVP and/or chloroquine with 1 mM 3-isob utyl-I-methylxanthine (IBMX) and cAMP concentrations were measured by radio immunoassay. To establish the possible site of interference in cAMP product ion IMCD segments were incubated in the presence of chloroquine and forskol in. Chloroquine at concentrations ranging from 10(-9) M to 10(-6) M did not affect cAMP production by comparison with control. However, AVP (10(-8) M) and forskolin (10(-6) M) significantly (p < 0.01) increased cAMP accumulat ion. Chloroquine at all concentrations significantly suppressed the AVP sti mulated cAMP production (e.g., chloroquine (10(-8) M) + AVP (10(-8) M) 41 /- 12 fmol/4 mm (n = 9 tubules) vs. AVP (10(-8) M) alone 82 +/- 9 fmol/4 mi n/mm (n = 37 tubules). Chloroquine at all concentrations tested did not hav e any effect an forskolin-induced cAMP production. The data suggest that ch loroquine inhibits the AVP induced cAMP production at the level of hormone/ receptor complex. This possibly explains the previously reported lack of th e normal antidiuretic responses of AVP in rats following chloroquine admini stration.