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Activation of multiple intracellular transduction signals by vasopressin in vasopressin‐sensitive neurones of the rat supraoptic nucleus
Author(s) -
Sabatier Nancy,
Richard Philippe,
Dayanithi Govindan
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.699ba.x
Subject(s) - vasopressin , phospholipase c , calphostin c , supraoptic nucleus , medicine , endocrinology , ibmx , phosphodiesterase inhibitor , protein kinase a , protein kinase c , arginine vasopressin receptor 1b , biology , adenylate kinase , vasopressin receptor , chemistry , signal transduction , kinase , microbiology and biotechnology , forskolin , receptor , antagonist , stimulation
1 The intracellular mechanisms activated by the binding of vasopressin to its receptor(s) and which result in the increase of [Ca 2+ ] i were investigated in freshly dissociated supraoptic nucleus neurones. Various pharmacological agents were used to investigate the possible involvement of phospholipase C (PLC) and adenylate cyclase (AC) intracellular pathways in the transduction of the vasopressin action. 2 Both the PLC inhibitor U‐73122 and the protein kinase C (PKC) inhibitor calphostin C, reduced the [Ca 2+ ] i rise elicited by vasopressin. The cAMP analogue, 8‐Br‐cAMP produced an increase in [Ca 2+ ] i and IBMX, a phosphodiesterase inhibitor, potentiated the response to vasopressin. 3 After pre‐incubation with the AC inhibitor SQ‐22536, 7 out of 18 vasopressin‐sensitive neurones showed no inhibition of the vasopressin response, while the response to vasopressin was reduced by greater than 35 % in each of the other 11 neurones. 4 The activation of protein kinase A (PKA) with Sp‐cAMPS caused an increase in [Ca 2+ ] i which was additive to the vasopressin‐elicited [Ca 2+ ] i increase. After incubation with the PKA inhibitors Rp‐cAMPS or H‐89, the [Ca 2+ ] i responses triggered by Sp‐cAMPS and vasopressin were, respectively, abolished and greatly reduced. 5 A combined administration of SQ‐22536 (AC inhibitor) followed by U‐73122 (PLC inhibitor), or U‐73122 followed by H‐89 (PKA inhibitor), virtually abolished the response to vasopressin. 6 In vasopressin‐responsive neurones, the pituitary adenylate cyclase‐activating polypeptide (PACAP) induced a [Ca 2+ ] i increase similar to the response to vasopressin and in both cases the increase was inhibited to the same extent by a combination of U‐73122 and Rp‐cAMPS. 7 In conclusion, we suggest that the autoregulation exerted specifically by vasopressin on vasopressin‐sensitive neurones involves the activation of both PLC‐ and AC‐linked pathways.