Ali Hassan

A.M.A. Hassan & D.R. Mason

Department of Zoology, University of Canterbury, Christchurch, New Zealand.

Recently we have shown that treatment of ovine anterior pituitary cells with AVP, an important regulator of ACTH secretion, results in a desensitization to a subsequent stimulation with AVP. This desensitization was rapid and readily reversible, suggesting that it might be mediated by receptor phosphorylation. Recovery from such desensitization is thought to involve receptor internalization and subsequent dephosphorylation by protein phosphatases. The aim of this study was to investigate the involvement of these processes in the resensitization of the ACTH response to AVP. Using a multi-column perifusion system dispersed ovine anterior pituitary cells were stimulated with a 5 min 100 nM AVP pulse. When this pulse was immediately preceded by a 15 min pre-treatment with 10 nM the response to it was reduced by 55.8 ?? 2.6% (n=18, p<0.01, ANOVA with Dunnett’s test). When a ‘recovery period’ was allowed between the pulse and the pre-treatment resensitization occurred; recovery was complete after 20 min. Blockade of receptor internalization by treatment with 0.25 mg/ml concanavalin A or 0.4 M sucrose for 70 min prior to the 100 nM AVP pulse reduced the extent of desensitization induced by AVP pre-treatment rather than preventing resensitization. Inhibition of protein phosphatase 1 and 2A activity with 10 nM okadaic acid had no effect on either resensitization or desensitization. Treatment with 1000 nM FK506, which specifically inhibits protein phosphatase 2B (PP2B), attenuated resensitization: recovery from desensitization was not complete until 40 min. These results suggest that desensitization of the ACTH response to AVP requires receptor internalization and that resensitization is dependent upon PP2B activity.

New Zealand Medical Journal 115:176, 2002.

Presented at the Canterbury Medical Research Society Scientific Meeting, Christchurch, New Zealand, 2001.