CHLOROQUINE INHIBITS ARGININE VASOPRESSIN PRODUCTION IN ISOLATED RAT INNER MEDULLARY SEGMENTS INDUCED cAMP COLLECTING DUCT

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Previous studies showed that acute chloroquine administration increases plasma arginine vasopressin (AVP) concentration in the rat without influencing urine flow rate. The present study was designed to investigate whether chloroquine inhibits the AVP-induced cAMP production that mediates the antidiuretic effects of vasopressin. Single inner medullary collecting duct (IMCD) segments were pre-incubated at 35°C for 10 min followed by 4 min at 37° C with combinations of AVP and/or chloroquine with 1 mM 3-isobutyl-I-methylxanthine (IBMX) and cAMP concentrations were measured by radioimmunoassay. To establish the possible site of interference in cAMP production IMCD segments were incubated in the presence of chloroquine and forskolin. 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 accumulation. Chloroquine at all concentrations significantly suppressed the AVP stimulated 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 min/mm (n = 37 tubules. Chloroquine at all concentrations tested did not have any effect an forskolin-induced cAMP production. The data suggest that chloroquine inhibits the AVP induced cAMP production at the level of hormone/receptor complex. This possibly explains the previously reported lack of the normal antidiuretic responses of AVP in rats following chloroquine administration.