scholarly journals Short-Term Plasticity of Cyclic Adenosine 3′,5′-Monophosphate Signaling in Anterior Pituitary Corticotrope Cells: The Role of Adenylyl Cyclase Isotypes

2003 ◽  
Vol 17 (4) ◽  
pp. 692-703 ◽  
Author(s):  
Ferenc A. Antoni ◽  
Alexander A. Sosunov ◽  
Anders Haunsø ◽  
Janice M. Paterson ◽  
James Simpson
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Anterior Pituitary ◽  
Feedback Regulation ◽  
Pituitary Cells ◽  
Adenylyl Cyclases ◽  
Physiological Control ◽  
Negative Feedback Regulation ◽  
Phorbol Dibutyrate ◽  
Kinase C

Abstract Anterior pituitary corticotropes show a wide repertory of responses to hypothalamic neuropeptides and adrenal corticosteroids. The hypothesis that plasticity of the cAMP signaling system underlies this adaptive versatility was investigated. In dispersed rat anterior pituitary cells, depletion of intracellular Ca2+ stores with thapsigargin combined with ryanodine or caffeine enhanced the corticotropin releasing-factor (CRF)-evoked cAMP response by 4-fold, whereas reduction of Ca2+ entry alone had no effect. CRF-induced cAMP was amplified 15-fold by arginine-vasopressin (AVP) or phorbol-dibutyrate ester. In the presence of inhibitors of cyclic nucleotide phosphodiesterases and phorbol-dibutyrate ester, the depletion of Ca2+ stores had no further effect on CRF-induced cAMP accumulation. Adenohypophysial expression of mRNAs for the Ca2+-inhibited adenylyl cyclases (ACs) VI and IX, and the protein kinase C-stimulated ACs II and VII was demonstrated. ACIX was detected in corticotropes by immunocytochemistry, whereas ACII and ACVI were not present. The data show negative feedback regulation of CRF-induced cAMP levels by Ca2+ derived from ryanodine receptor-operated intracellular stores. Stimulation of protein kinase C by AVP enhances Ca2+-independent cAMP synthesis, thus changing the characteristics of intracellular Ca2+ feedback. It is proposed that the modulation of intracellular Ca2+ feedback in corticotropes by AVP is an important element of physiological control.

scholarly journals Mechanisms of desensitization of the adrenocorticotropin response to arginine vasopressin in ovine anterior pituitary cells

2005 ◽  
Vol 184 (1) ◽  
pp. 29-40 ◽  
Author(s):  
A Hassan ◽  
D Mason
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Phosphatase ◽  
Anterior Pituitary ◽  
Receptor Internalization ◽  
Pituitary Cells ◽  
Acth Secretion ◽  
Kinase C ◽  
Anterior Pituitary Cells ◽  
Vasopressin Receptors

Arginine vasopressin (AVP) stimulates adrenocorticotropin (ACTH) secretion from corticotroph cells of the anterior pituitary via activation of the V1b vasopressin receptor, a member of the G protein-coupled receptor (GPCR) family. Recently, we have shown that treatment of ovine anterior pituitary cells with AVP for short periods results in reduced responsiveness to subsequent stimulation with AVP. The aim of this study was to investigate mechanisms involved in this desensitization process. Among the GPCR family, rapid desensitization is commonly mediated by receptor phosphorylation, with resensitization being mediated by internalization and subsequent dephosphorylation of the receptors by protein phosphatases. Since desensitization of V1a vasopressin receptors is mediated by protein kinase C-mediated receptor phosphorylation, we investigated the involvement of this enzyme in desensitization of the ACTH response to AVP. Treatment of perifused ovine anterior pituitary cells with the specific protein kinase C (PKC) activator 1,2-dioctanoyl-sn-glycerol (300 μM) did not induce any reduction in response to a subsequent 5-min stimulation with 100 nM AVP, despite potently stimulating ACTH secretion. Likewise, the results obtained using the PKC inhibitor Ro 31-8220 were not consistent with involvement of PKC in AVP desensitization: 2 μM Ro 31-8220 did not reduce the ability of a 10 nM AVP pretreatment to induce desensitization to a subsequent stimulation with 100 nM AVP. Pharmacologic blockade of receptor internalization by treatment with 0.25 mg/ml concanavalin A significantly impaired the ability of a 15-min pretreatment with 10 nM AVP to induce desensitization, rather than affecting resensitization. Treatment with 10 nM okadaic acid, an inhibitor of protein phosphatase 1 and 2A, had no effect on either resensitization or desensitization. In contrast, inhibition of protein phosphatase 2B (PP2B) with 1 μM FK506 decreased the rate of resensitization: complete recovery from desensitization took 40 min, whereas in controls recovery was complete 20 min after termination of the pretreatment. These results indicate that desensitization of the ACTH response to AVP is not mediated by PKC-catalyzed phosphorylation, suggesting subtype-specific differences in the regulation of V1a and V1b vasopressin receptors. The data demonstrate that desensitization was dependent, at least in part, upon receptor internalization and that resensitization was dependent upon PP2B-mediated receptor dephosphorylation.

Intracellular mechanisms involved in the stimulation of growth hormone release from rat anterior pituitary cells by Russell's viper venom

1990 ◽  
Vol 127 (1) ◽  
pp. 111-117 ◽  
Author(s):  
G. R. Hart ◽  
G. Caldwell ◽  
J. M. Burrin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Kinase C ◽  
Anterior Pituitary Cells ◽  
Russell’S Viper ◽  
Intracellular Mechanisms

ABSTRACT We have previously shown that a heat-stable component of Russell's viper venom (RVV) releases GH in a dose-dependent manner from cultured rat anterior pituitary cells. We have now investigated the intracellular mechanisms involved in RVV-stimulated GH release by concomitant administration of RVV with known intracellular mediators in rat pituitary cells. 3-Isobutyl-1-methylxanthine (IBMX; 0·5 mmol/l), added to cultured rat anterior pituitary cells simultaneously with RVV, at concentrations up to a maximally effective dose of 10 μg/ml, increased GH release (3·7-fold, 4·0-fold and 2·0-fold; P < 0·001) compared with the effect of venom alone. These effects were additive, indicating that RVV and IBMX stimulate through different intracellular messengers. RVV failed to increase the formation of basal or IBMX-stimulated intracellular cyclic AMP (cAMP), confirming that RVV affects GH release through a cAMP-independent pathway. 12-0-Tetradecanoylphorbol-13-acetate (TPA; 0·1 μmol/l), added simultaneously with various doses of RVV (0·1–10 μg/ml), did not increase GH release beyond the maximal effect of RVV. This result indicates that RVV might be stimulating GH release through a similar mechanism to that of TPA (by activating protein kinase C). When pituitary cells were perifused with Ca2+-free medium or verapamil (50 μmol/l), RVV-stimulated GH release was inhibited by 65 and 42% respectively. This reflects the recognized requirement of Ca2+ for secretory processes. However, RVV (10 μg/ml) had no significant effect on intracellular free Ca2+ concentrations as measured using the fluorescent Ca2+ probe quin-2. These findings indicate that the mechanism of action of RVV on GH release is independent of a change in both cAMP levels and intracellular free Ca2+ concentrations, and is dependent upon protein kinase C. Journal of Endocrinology (1990) 127, 111–117

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