Ali Hassan

Ali Hassan & Drusilla Mason

Department of Zoology, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.

Treatment of anterior pituitary cells with AVP results in a desensitization of the ACTH response to a subsequent AVP stimulation. This desensitization is rapid and readily reversible, suggesting that it is mediated by receptor phosphorylation. Since recovery from such desensitization is thought to involve receptor internalization and subsequent dephosphorylation by protein phosphatases we investigated the involvement of these processes in resensitization of the ACTH response to AVP. Perifused ovine anterior pituitary cells were stimulated with a 5 min pulse of 100 nM AVP. The response to this pulse was reduced by 55.8 ± 2.6% if it was immediately preceded by a 15 min pretreatment with 10 nM AVP. When a recovery period of variable duration was allowed between the pretreatment and the pulse resensitization occurred. Recovery was complete within 20 min. Inhibition of receptor internalization by treatment with 0.25 mg/ml concanavalin A for 70 min prior to the AVP pulse reduced the extent of desensitization induced by AVP pretreatment but did not affect resensitization. Inhibition of protein phosphatase 2B (PP2B) with 1 μM FK506 decreased the rate of resensitization. Complete recovery from desensitization took 40 min. Treatment with the protein phosphatase 1 and 2A inhibitor okadaic acid (10 nM) had no effect. These results suggest that desensitization of the ACTH response to AVP requires receptor internalization and that resensitization is dependent upon PP2B-mediated receptor dephosphorylation.

Supported by the Canterbury Medical Research Foundation and the University of Canterbury.

Experimental Biology 2003, San Diego, CA, Abstract 6999, 2003.