PMID- 11171601 OWN - NLM STAT- MEDLINE DCOM- 20010322 LR - 20181130 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 280 IP - 3 DP - 2001 Mar TI - Desensitization of angiotensin II: effect on [Ca2+]i, inositol triphosphate, and prolactin in pituitary cells. PG - E462-70 AB - Activation of pituitary angiotensin (ANG II) type 1 receptors (AT1) mobilizes intracellular Ca2+, resulting in increased prolactin secretion. We first assessed desensitization of AT1 receptors by testing ANG II-induced intracellular Ca2+ concentration ([Ca2+](i)) response in rat anterior pituitary cells. A period as short as 1 min with 10(-7) M ANG II was effective in producing desensitization (remaining response was 66.8 +/- 2.1% of nondesensitized cells). Desensitization was a concentration-related event (EC(50): 1.1 nM). Although partial recovery was obtained 15 min after removal of ANG II, full response could not be achieved even after 4 h (77.6 +/- 2.4%). Experiments with 5 x 10(-7) M ionomycin indicated that intracellular Ca2+ stores of desensitized cells had already recovered when desensitization was still significant. The thyrotropin-releasing hormone (TRH)-induced intracellular Ca2+ peak was attenuated in the ANG II-pretreated group. ANG II pretreatment also desensitized ANG II- and TRH-induced inositol phosphate generation (72.8 +/- 3.5 and 69.6 +/- 6.1%, respectively, for inositol triphosphate) and prolactin secretion (53.4 +/- 2.3 and 65.1 +/- 7.2%), effects independent of PKC activation. We conclude that, in pituitary cells, inositol triphosphate formation, [Ca2+](i) mobilization, and prolactin release in response to ANG II undergo rapid, long-lasting, homologous and heterologous desensitization. FAU - Gonzalez Iglesias, A AU - Gonzalez Iglesias A AD - Instituto de Biologia y Medicina Experimental-Consejo Nacional de Investigaciones Cientificas y Tecnicas, 1428 Buenos Aires, Argentina. FAU - Suarez, C AU - Suarez C FAU - Feierstein, C AU - Feierstein C FAU - Diaz-Torga, G AU - Diaz-Torga G FAU - Becu-Villalobos, D AU - Becu-Villalobos D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Receptor, Angiotensin, Type 1) RN - 0 (Receptor, Angiotensin, Type 2) RN - 0 (Receptors, Angiotensin) RN - 11128-99-7 (Angiotensin II) RN - 56092-81-0 (Ionomycin) RN - 5Y5F15120W (Thyrotropin-Releasing Hormone) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - 9002-62-4 (Prolactin) RN - EC 2.7.11.13 (Protein Kinase C) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SY7Q814VUP (Calcium) SB - IM MH - Angiotensin II/*pharmacology MH - Animals MH - Calcium/*metabolism MH - Cells, Cultured MH - Drug Tolerance MH - Female MH - Inositol 1,4,5-Trisphosphate/*metabolism MH - Ionomycin/pharmacology MH - Pituitary Gland, Anterior/*drug effects/*metabolism MH - Prolactin/*metabolism MH - Protein Kinase C/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Angiotensin, Type 1 MH - Receptor, Angiotensin, Type 2 MH - Receptors, Angiotensin/drug effects/physiology MH - Tetradecanoylphorbol Acetate/pharmacology MH - Thyrotropin-Releasing Hormone/pharmacology EDAT- 2001/02/15 11:00 MHDA- 2001/03/27 10:01 CRDT- 2001/02/15 11:00 PHST- 2001/02/15 11:00 [pubmed] PHST- 2001/03/27 10:01 [medline] PHST- 2001/02/15 11:00 [entrez] AID - 10.1152/ajpendo.2001.280.3.E462 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2001 Mar;280(3):E462-70. doi: 10.1152/ajpendo.2001.280.3.E462.