Pituitary adenylate cyclase activating polypeptide (PACAP) potently enhances tyrosine hydroxylase (TH) expression in adrenal chromaffin cells

Rius, R.A.; Guidotti, Alessandro; Costa, E.

doi:10.1016/0024-3205(94)00614-8

Cited by 44 publications

(21 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PACAP, in addition to stimulating catecholamine secretion, potently activates TH in chromaffin cell cultures (34)(35). Consistent with these in vitro studies, PACAP-deficient mice failed to respond to insulin with an induction of TH enzymatic activity.…”

Section: Discussionsupporting

confidence: 67%

“…The present findings provide a physiological context for previous observations that PACAP and related peptides mimic, in perfused adrenal gland or adrenomedullary cells in culture, the sustained catecholamine secretion, and compensatory stimulation of catecholamine biosynthesis, that follows sustained splanchnic nerve firing during long-term metabolic stress (7,34,36) PACAP, in keeping with a general role for neuropeptides in stress and disease (37), thus performs an emergency response function in the paraphysiological regulation of the sympathoadrenal axis during metabolic stress.…”

Section: Discussionmentioning

confidence: 86%

See 1 more Smart Citation

Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis

Hamelink

Tjurmina

Damadzic

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

237

241

View full text Add to dashboard Cite

The adrenal gland is important for homeostatic responses to metabolic stress: hypoglycemia stimulates the splanchnic nerve, epinephrine is released from adrenomedullary chromaffin cells, and compensatory glucogenesis ensues. Acetylcholine is the primary neurotransmitter mediating catecholamine secretion from the adrenal medulla. Accumulating evidence suggests that a secretin-related neuropeptide also may function as a transmitter at the adrenomedullary synapse. Costaining with highly specific antibodies against the secretin-related neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and the vesicular acetylcholine transporter (VAChT) revealed that PACAP is found in nerve terminals at all mouse adrenomedullary cholinergic synapses. Mice with a targeted deletion of the PACAP gene had otherwise normal cholinergic innervation and morphology of the adrenal medulla, normal adrenal catecholamine and blood glucose levels, and an intact initial catecholamine secretory response to insulin-induced hypoglycemia. However, insulin-induced hypoglycemia was more profound and longer-lasting in PACAP knock-outs, and was associated with a dose-related lethality absent in wildtype mice. Failure of PACAP-deficient mice to adequately counterregulate plasma glucose levels could be accounted for by impaired long-term secretion of epinephrine, secondary to a lack of induction of tyrosine hydroxylase, normally occurring after insulin hypoglycemia in wild-type mice, and a consequent depletion of adrenomedullary epinephrine stores. Thus, PACAP is needed to couple epinephrine biosynthesis to secretion during metabolic stress. PACAP appears to function as an ''emergency response'' cotransmitter in the sympathoadrenal axis, where the primary secretory response is controlled by a classical neurotransmitter but sustained under paraphysiological conditions by a neuropeptide. T he adrenal medulla has been used extensively as a model for understanding basic features of neurotransmission and transsynaptic regulation, because of the simplicity of its synaptic inputs and the physiological importance and ease of measurement of catecholamine secretion as a final output (1). Recently, the adrenomedullary synapse has been the focus of analysis of the functional meaning of classical neurotransmitter and neuropeptide coexpression and corelease at mammalian synapses (2). Acetylcholine is the primary neurotransmitter mediating catecholamine secretion from the adrenal medulla (3). A second noncholinergic neurotransmitter also is thought to be involved in sympathoadrenal function because acetylcholine, or cholinergic agonists alone, cannot mimic the prolonged secretion and robust stimulation of catecholamine biosynthesis elicited by electrical stimulation of the splanchnic innervation of the adrenal medulla (4-7). It has been proposed that pituitary adenylate cyclaseactivating peptide (PACAP) or a PACAP-related neuropeptide acts as a cotransmitter with acetylcholine at the adrenomedullary synapse, based on neuroanatomical evidence obtained in v...

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 86%

Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis

Hamelink

Tjurmina

Damadzic

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

237

241

View full text Add to dashboard Cite

show abstract

“…Concurrently, in bovine and human, PACAP increases calcium levels from ryanodine/caffeine-sensitive calcium stores (Houchi et al, 1995;Tanaka et al, 1996Tanaka et al, , 1998Shibuya et al, 1999;Payet et al, 2003). The effect of PACAP on catecholamine release is associated with an increase in the expression of tyrosine hydroxylase, dopamine ␤-hydroxylase, and phenylethanolamine N-methyltransferase (Houchi et al, 1994;Rius et al, 1994;Isobe et al, 1996;Marley et al, 1996;Tönshoff et al, 1997;Hong et al, 1998;Choi et al, 1999;Park et al, 1999). It has been shown that the stimulatory effect of PACAP on tyrosine hydroxylase activity is mediated through activation of the AC/PKA transduction pathway (Marley et al, 1996) and can be accounted for by phosphorylation of TH at Ser 40 (Bobrovskaya et al, 2007).…”

Section: E Effects Of Pituitary Adenylate Cyclase-activating Polypepmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

View full text Add to dashboard Cite

“…Regulation of inositol phosphate (IP) production by coupling to PLCβ through Gq is more efficacious in PAC1hop and null compared to hip receptors as assessed in non-neural heterologous cells [27, 46, 54]. The functional importance of Gs/AC- and Gq/PLCβ-mediated combinatorial signaling has been shown for sustained release of catecholamines (CAs) and neuropeptides from adrenomedullary chromaffin cells (CCs) [5, 16, 29, 49, 63], which predominantly express the PAC1hop receptor variant [38, 40]. In the adrenomedullary pheochromocytoma PC12 cell line [14] it has been shown that PAC1hop-activated sustained CA release proceeds through inositol-1,4,5-trisphosphate (IP 3 )-mediated Ca 2+ release from intracellular stores and store-operated Ca 2+ entry (SOCE) [39, 58].…”

Section: Introductionmentioning

confidence: 99%

PAC1hop, null and hip receptors mediate differential signaling through cyclic AMP and calcium leading to splice variant-specific gene induction in neural cells

2011

View full text Add to dashboard Cite

Pituitary adenylate cyclase-activating polypeptide (PACAP)-mediated activation of its G protein-coupled receptor PAC1 results in activation of the two G proteins Gs and Gq to alter second messenger generation and gene transcription in the nervous system, important for homeostatic responses to stress and injury. Heterologous expression of the three major splice variants of the rat PAC1 receptor, PAC1hop, null and hip, in neural NG108-15 cells conferred PACAP-mediated intracellular cAMP generation, while elevation of [Ca2+]i occurred only in PAC1hop-, and to a lesser extent in PAC1null-expressing cells. Induction of vasoactive intestinal polypeptide (VIP) and stanniocalcin 1 (STC1), two genes potentially involved in PACAP’s homeostatic responses, was examined as a function of the expressed PAC1 variant. VIP induction was greatest in PAC1hop-expressing cells, suggesting that a maximal transcriptional response requires combinatorial signaling through both cAMP and Ca2+. STC1 induction was similar for all three receptor splice variants and was mimicked by the adenylate cyclase activator forskolin, indicating that cAMP elevation is sufficient to induce STC1. The degree of activation of two different second messenger pathways appears to determine the transcriptional response, suggesting that cellular responses to stressors are fine-tuned through differential receptor isoform expression. Signaling to the VIP gene proceeded through cAMP and protein kinase A (PKA) in these cells, independently of the MAP kinase ERK1/2. STC1 gene induction by PACAP was dependent on cAMP and ERK1/2, independently of PKA. Differential gene induction via different cAMP dependent signaling pathways potentially provides further targets for the design of treatments for stress-associated disorders.

show abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) potently enhances tyrosine hydroxylase (TH) expression in adrenal chromaffin cells

Cited by 44 publications

References 22 publications

Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis

Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

PAC1hop, null and hip receptors mediate differential signaling through cyclic AMP and calcium leading to splice variant-specific gene induction in neural cells

Contact Info

Product

Resources

About