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Interactions of antidiuretic hormone (ADH) and prostaglandin (PG)
PROSTAGLANDINS
INTERACTIONS OF ANTIDIURETIC HORMONE (ADH) AND PROSTAGLANDIN (PG) SCHLONDORFF, D. Albert Einstein College of Medicine - Bronx, New York U.S.A. Prostaglandin PGE8 inhibits the hydroosmotic effect of ADH. ADH increases CAMP production and concomnitantlymay also enhance PG synthesis by activatino phospholipase. The PGE8 generated decreases CAMP production, closing a negative feed-back loop. On the other hand, in several systems, CAMP influences PG production by inhibiting phospholipase. We therefore examined the effect of 8-bromo CAMP and IBMX, a phosphodiesterase inhibitor. on PGE, svnthesis bv eoithelial cells from toad bladder. Both CAMP and IBMX fignificantly"inhibited PGE synthesis. 4 n of IBMX on This may provide an additional explanation for the act1 ADH. ADH also increased the turnover of phosphatidylinositolwhich was also suppressed by IBMX. Thus it appears that ADH enhances CAMP generation and phosphatidylinositol turnover. The PGE generated will inhibit CAMP production, while CAMP in turn will inhl it phospholipase and hence PGE synthesis. Thus a double reciprocal feed-back mechanism may exisz preventing an overshoot of the response in either direction.
*2*
We also reexamined the effect of exogenous PGE2 on ADH's action in the toad bladder. To eliminate endogenous PGE2, tissues were pretreated with cyclooxygenase inhibitors. In response to ADH both water flow and the in vitro activation of CAMP dependent protein-kinase, a reflection of the cellular CAMP concentration, were enhanced after PG inhibition, consistent with inhibition of ADH-induced CAMP production by PG. On the other hand, exogenous PGE8 also increased CAMP content and kinase activation, but did not increase water flow. Accordinoly PGE dissociates CAMP and kinase activation from the hydroosmotic resp8nse, suggesting that PGE also inhibits steps distal to CAMP. Consistent with this PGE8 (ID-&o 10%) decreased the response to submaximal CAMP (5mM) or 8-bromo-CAMP (0.03 mM) in bladders pretreated with cyclooxygenase inhibitors. Thus ADH and PGE2 interact both at the site of CAMP generation and also at steps distal to or different from CAMP production.
68
SUPPLEMENT TO VOL. 27
INTERACTIONS OF ANTIDIURETIC HORMONE (ADH) AND PROSTAGLANDIN (PG) SCHLONDORFF, D. Albert Einstein College of Medicine - Bronx, New York U.S.A. Prostaglandin PGE8 inhibits the hydroosmotic effect of ADH. ADH increases CAMP production and concomnitantlymay also enhance PG synthesis by activatino phospholipase. The PGE8 generated decreases CAMP production, closing a negative feed-back loop. On the other hand, in several systems, CAMP influences PG production by inhibiting phospholipase. We therefore examined the effect of 8-bromo CAMP and IBMX, a phosphodiesterase inhibitor. on PGE, svnthesis bv eoithelial cells from toad bladder. Both CAMP and IBMX fignificantly"inhibited PGE synthesis. 4 n of IBMX on This may provide an additional explanation for the act1 ADH. ADH also increased the turnover of phosphatidylinositolwhich was also suppressed by IBMX. Thus it appears that ADH enhances CAMP generation and phosphatidylinositol turnover. The PGE generated will inhibit CAMP production, while CAMP in turn will inhl it phospholipase and hence PGE synthesis. Thus a double reciprocal feed-back mechanism may exisz preventing an overshoot of the response in either direction.
*2*
We also reexamined the effect of exogenous PGE2 on ADH's action in the toad bladder. To eliminate endogenous PGE2, tissues were pretreated with cyclooxygenase inhibitors. In response to ADH both water flow and the in vitro activation of CAMP dependent protein-kinase, a reflection of the cellular CAMP concentration, were enhanced after PG inhibition, consistent with inhibition of ADH-induced CAMP production by PG. On the other hand, exogenous PGE8 also increased CAMP content and kinase activation, but did not increase water flow. Accordinoly PGE dissociates CAMP and kinase activation from the hydroosmotic resp8nse, suggesting that PGE also inhibits steps distal to CAMP. Consistent with this PGE8 (ID-&o 10%) decreased the response to submaximal CAMP (5mM) or 8-bromo-CAMP (0.03 mM) in bladders pretreated with cyclooxygenase inhibitors. Thus ADH and PGE2 interact both at the site of CAMP generation and also at steps distal to or different from CAMP production.
68
SUPPLEMENT TO VOL. 27