title: Angiotensin and calcium signaling in the pituitary and hypothalamus.
abstract: 1) In the rat pituitary, angiotensin type 1B receptors (AT1B) are located in lactotrophs and corticotrophs. 2) Activation of AT1B receptors are coupled to Gq/11 (Guanine protein coupled receptor, or GPCR); they increase phospholipase beta C (PLC) activity resulting in inositol 1,4,5 triphosphate (InsP3) and diacylglycerol (DAG) formation. A biphasic increase in [Ca2+]i triggered by InsP3 and DAG ensues. 3) As many GPCRs, AT1B pituitary receptors rapidly desensitize. 4) This was observed in the generation of InsP3, the mobilization of intracellular Ca(2+), and in prolactin release. Both homologous and heterologous desensitization was evidenced. 5) Desensitization of the angiotensin II type 1 (AT1) receptor in the pituitary shares similarities and differences with endogenously expressed or transfected AT1 receptors in different cell types. 6) In the pituitary hyperplasia generated by chronic estrogen treatment there was desensitization or alteration in angiotensin II (Ang II) evoked intracellular Ca2+ increase, InsP3 generation, and prolactin release. This correlates with a downregulation of AT1 receptors. 7) In particular, in hyperplastic cells Ang II failed to evoke a transient acute peak in [Ca2+]i, which was replaced by a persistent plateau phase of [Ca2+]i increase. 8) Different calcium channels participate in Ang II induced [Ca2+]i increase in control and hyperplastic cells. While spike phase in control cells is dependent on intracellular stores sensitive to thapsigargin, in hyperplastic cells plateau increase is dependent on extracellular calcium influx. 9) Signal transduction of the AT1 pituitary receptor is greatly modified by hyperplasia, and it may be an important mechanism in the control of the hyperplastic process. 10) In the hypothalamus and brain stem there is a predominant expression of AT1A and AT2 mRNA. 11) Ang II acts at specific receptors located on neurons in the hypothalamus and brain stem to elicit alterations in blood pressure, fluid intake, and hormone secretion. 12) Calcium channels play important roles in the Ang II induced behavioral and endocrine responses. 13) Ang II, in physiological concentrations, can activate AT1 receptors to stimulate both Ca2+ release from intracellular stores and Ca2+ influx from the extracellular space to increase [Ca2+]i in polygonal and stellate astroglia of the hypothalamus and brain stem. 14) In primary cell culture of neurons from newborn rat hypothalamus and brain stem, it has also been determined that Ang II elicits an AT1 receptor mediated inhibition of delayed rectifier K(+) current and a stimulation of Ca2+ current. 15) In primary cell cultures derived from the subfornical organ or the organum vasculosum laminae terminalis of newborn rat pups, Ang II produced a pronounced desensitization of the [Ca2+]i response. 16) Hypothalamic and pituitary Ang II systems are involved in different functions, some of which are related. At both levels Ang II signals through [Ca2+]i in a characteristic way.
authors.affiliation: Instituto de Biología y Medicina Experimental, CONICET, V. Obligado 2490, Buenos Aires, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Suárez
authors.forename: Isabel García
authors.initials: IG
authors.lastname: Tornadú
authors.forename: Carolina
authors.initials: C
authors.lastname: Cristina
authors.forename: Jorge
authors.initials: J
authors.lastname: Vela
authors.forename: Arturo González
authors.initials: AG
authors.lastname: Iglesias
authors.forename: Carlos
authors.initials: C
authors.lastname: Libertun
authors.forename: Graciela
authors.initials: G
authors.lastname: Díaz-Torga
authors.forename: Damasia
authors.initials: D
authors.lastname: Becu-Villalobos
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism*
chemical_list: D010907:Pituitary Hormones; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II