Protein Kinase C and Phospholipase C Mediate α‐ and β‐Adrenoceptor Intercommunication in Rat Hypothalamic Slices

Petitti, Nicolas; Etgen, Anne M.

doi:10.1111/j.1471-4159.1991.tb08196.x

Cited by 24 publications

(16 citation statements)

References 58 publications

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“…These products in turn activate protein kinase C (PKC) and induce calcium influx, respectively. Because ai-re ceptors appear to augment cAMP formation by a cascade involving Gp-phospholipase C-PKC activation [36][37][38], Pg could modify one or more of these molecular compo nents. Pg may affect the coupling between ai-adrenergic receptors and Gp or between Gp and the effector enzyme (phospholipase C).…”

Section: Discussionmentioning

confidence: 99%

Progesterone Promotes Rapid Desensitization of α<sub>1</sub>-Adrenergic Receptor Augmentation of cAMP Formation in Rat Hypothalamic Slices

Petitti¹,

Etgen²

1992

Neuroendocrinology

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We previously demonstrated that norepinephrine (NE) induction of cAMP accumulation in slices of the preoptic area (POA) and middle hypothalamus (MH) is reduced by in vivo administration of progesterone to estradiol-primed rats, apparently by eliminating α₁-receptor augmentation of β-receptor-stimulated cAMP formation. The present studies examined whether in vitro exposure to progesterone would also depress NE-stimulated cAMP synthesis. POA and MH slices from estradiol-primed females were incubated with 20 nM progesterone for 5-30 min prior to addition of 100 µM NE. Pre-incubation of slices with progesterone for as little as 5 min significantly suppressed NE-stimulated cAMP formation by greater than 60%. This effect was estrogen-dependent in that progesterone in vitro did not inhibit NE-stimulated cAMP accumulation in slices from ovariectomized rats not pretreated with estradiol. Isoproterenol, a β-adrenergic agonist, elevated cAMP to the same extent in slices from estradiol-primed females incubated with and without progesterone in vitro; however, the α₁-agonist, phenylephrine, was unable to augment cAMP formation in slices incubated in vitro with progesterone for 5 min prior to drug challenge. To determine whether the rapid effects of progesterone may be exerted at the level of the plasma membrane, we employed progesterone conjugated to bovine serum albumin at carbon 3 (P-3-BSA). Slices from estradiol-primed rats incubated with P-3-BSA for 5 min did not exhibit an α₁-receptor augmentation of β-receptor-stimulated cAMP accumulation. These data indicate that progesterone may have rapid, non-genomic effects on α₁-adrenergic receptor coupling to second-messenger systems in the hypothalamus of female rats.

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Section: Discussionmentioning

confidence: 99%

Progesterone Promotes Rapid Desensitization of α<sub>1</sub>-Adrenergic Receptor Augmentation of cAMP Formation in Rat Hypothalamic Slices

Petitti¹,

Etgen²

1992

Neuroendocrinology

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“…However, α 1B -ARs may also couple to other G proteins, including G h [53], G s [54,55], and G i /G o [56]. Compelling evidence that α 1B -ARs can activate other effectors, including mitogen-activated protein kinase (MAPK) pathway [57,58], cAMP [54,59], phospholipase D (PLD) [55] and PLA 2 [56,60]. The phosphorylation of activated adrenoceptors by G-protein-activated receptor kinases (GRKs) is followed by the binding of arrestin, which may prevent further G protein activation and downstream signaling [61].…”

Section: Molecular and Biophysical Studies Of Infl Uences On Sexual Amentioning

confidence: 99%

“…α 1B -ARs can also couple to G s , elevating intracellular cAMP and PKA [54,55]. However, the increase in cAMP is probably via a PKC-dependent potentiation of adenylyl cyclase activity [56,59].…”

Section: Molecular and Biophysical Studies Of Infl Uences On Sexual Amentioning

confidence: 99%

Hormone Effects on Specific and Global Brain Functions

Lee

Pfaff

2008

J. Physiol. Sci

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Abstract:The first demonstration of how biochemical changes in neurons in specific parts of the brain direct a complete mammalian behavior derived from the effects of estrogens in hypothalamic neurons that facilitate lordosis behavior, the primary reproductive behavior of female quadrupeds (Pfaff. Estrogens and Brain Function . 1980; Pfaff. Drive: Neurobiological and Molecular Mechanisms of Sexual Motivation. 1999). Sex behaviors depend on sexual arousal that in turn depends on a primitive function: generalized CNS arousal (Pfaff. Brain Arousal and Information Theory . 2006). Here we summarize one of the ways in which a generalized arousal transmitter, norepinephrine, can influence the electrical excitability of ventromedial hypothalamic cells in a way that will foster female sex behavior.Key words : estrogens, hypothalamus, sex, genomic, behavior. Neuroendocrinology began with work by G. Harris inOxford, M. Kawakami in Yokohama, C. Sawyer in Los Angeles, and others. That generation of neuroendocrinologists endeavored to explain how the brain regulates secretions from the pituitary, secretions that control the peripheral endocrine organs. We, in contrast, have worked to explain how hormones secreted from these peripheral organs influence brain activity in such a way as to regulate behavior. To review this work in reasonable length, we have contracted and modifi ed our contribution to the second edition of Hormones, Brain and Behavior and have concentrated on the transition from explaining a specifi c estrogen-facilitated sex behavior to the analysis of a global brain function, generalized CNS arousal.Our lab's research has proceeded through four steps to demonstrate how steroid hormone effects on nerve cells can direct natural, instinctive behaviors, as follows.First: Discovering exact cellular targets for steroid hormones in the brain. A system of hypothalamic and limbic forebrain neurons with sex hormone receptors, discovered in rodents [1, 2] was later found to be present in species ranging from fi sh through primates. This hormone-sensitive system apparently is a general feature of the vertebrate brain. In situ hybridization studies to distinguish gene expression for estrogen receptor alpha (ERalpha) from estrogen receptor beta (ER-beta) revealed remarkably different distributions for the two [3] and showed the estrogenic-feedback sensitivity of ER-alpha gene expression [4]. Hamada et al. [5] have visualized these ER-alpha-producing cells using modern transgenic techniques. In the ventromedial nucleus of the hypothalamus, not only ER-alpha, but also ER-beta mRNA can be downregulated by estradiol administration [6]. Musatov et al. [7] used an adeno-associated viral (AAV) vector encoding a small interfering RNA (siRNA) directed against the mRNA for ER-alpha and microinjected it into VMN with the result that proceptive and lordosis behaviors were abolished.Second: Working out the neural circuitry for hormonedependent female reproductive behavior, the fi rst behavior circuit elucidated for any mammal [8,9]. E...

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“…In rat brain slices, NE further increases cAMP synthesis by activating ␣ 1 -ARs, which are G q coupled and augment adenylyl cyclase activity via PKC (20). In rat brain slices, NE further increases cAMP synthesis by activating ␣ 1 -ARs, which are G q coupled and augment adenylyl cyclase activity via PKC (20).…”

Section: Effects Of Igf-i On Ne-stimulated Camp Accumulationmentioning

confidence: 99%

“…In many cases, including HYP and POA, the ␣ 1 -AR alone has no effect on adenylyl cyclase, but potentiates ␤-AR activation of cAMP synthesis (20). Adrenergic agonist-induced cAMP accumulation in brain slices was used as the marker of intracellular interaction among E 2 , IGF-I, and ARs.…”

mentioning

confidence: 99%

Insulin-Like Growth Factor-1 Regulation of α1-Adrenergic Receptor Signaling Is Estradiol Dependent in the Preoptic Area and Hypothalamus of Female Rats**This work was supported by Grants MH-41414, HD-29856, and T32-DK-07513. The data in this paper are from a thesis to be submitted by A.Q. in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Sue Golding Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY.

Quesada

Etgen²

2001

Endocrinology

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Recently, we demonstrated that estradiol (E(2)) modulates cross-talk between protein tyrosine kinases and norepinephrine (NE) receptor signaling in the hypothalamus (HYP) and preoptic area (POA), brain areas that govern female reproductive function. We are now investigating the identity of protein tyrosine kinase(s) that modify NE receptor signaling in the HYP and POA. Incubation of POA and HYP slices with insulin-like growth factor I (IGF-I), which signals via a receptor (IGF-IR) with endogenous tyrosine kinase activity, enhances NE-stimulated cAMP accumulation only in tissue derived from ovariectomized, E(2)-primed animals. JB-1, an antagonist for IGF-IR, prevents the IGF-I enhancement of NE-stimulated cAMP accumulation in both POA and HYP slices. IGF-I enhances NE-stimulated cAMP accumulation via modulation of alpha(1)-adrenoceptor potentiation of adenylyl cyclase. Binding studies in membranes demonstrate that ovariectomized, E(2)-primed animals show a significant increase in the density of [(125)I]IGF-I-binding sites in both POA and HYP compared with ovariectomized control animals. Neither the IC(50) for [(125)I]IGF-I displacement by IGF-I nor the levels of IGF-I binding proteins in serum or brain tissue are affected by E(2). RIA results showed that E(2) does not modify serum or brain IGF-I levels. These results indicate that E(2) regulation of NE receptor function in the POA and HYP involves increased expression of IGF-IR, and that after E(2) treatment, IGF-IR activation augments alpha(1)-adrenoceptor signaling.

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Protein Kinase C and Phospholipase C Mediate α‐ and β‐Adrenoceptor Intercommunication in Rat Hypothalamic Slices

Cited by 24 publications

References 58 publications

Progesterone Promotes Rapid Desensitization of α<sub>1</sub>-Adrenergic Receptor Augmentation of cAMP Formation in Rat Hypothalamic Slices

Progesterone Promotes Rapid Desensitization of α<sub>1</sub>-Adrenergic Receptor Augmentation of cAMP Formation in Rat Hypothalamic Slices

Hormone Effects on Specific and Global Brain Functions

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