Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study is to explore whether the renal and cardiovascular response to clonidine in type II diabetic patients is different from that in control subjects, and to clarify the role of central alpha 2-receptor in the regulation of cardiovascular response and sodium handling in type II diabetes mellitus (DM). Thirty-five diabetic inpatients aged 30-71 years (54.1 +/- 9.7) and ten control subjects (N) were enrolled in this study after their fasting plasma glucose had been improved. To evaluate the peripheral sympathetic nerve activity, 24-hour urinary catecholamine was measured, and pulse rate (PR) responses to a 30-second standing test was determined. On another day, blood pressure (BP), PR, plasma norepinephrine (PNE), cyclic AMP (p-cAMP), renin activity (PRA), aldosterone (PAC) and growth hormone (p-GH) were measured at 0, 30, 60, 90, 120, 150, 180 minutes following the oral administration of clonidine (150 micrograms). Type II DM were classified as DM with hyper-response (DM-HR, n = 12) when their PR decreased after clonidine more than that of N, and if not, they were classified as DM with normal response (DM-NR, n = 23). Urinary catecholamine excretions in type II DM were within the normal range. BP, PNE and p-cAMP were markedly decreased with clonidine in similar fashion in DM-NR, DM-HR and N. The percent changes of PNE were correlated positively with the changes of p-cAMP in both N and DM-NR (r = 0.660 and 0.449, respectively), but not in DM-HR. No significant difference in the changes of p-GH (delta p-GH) and integral of GH (the area under the curve) following clonidine administration was observed in the three groups. The decrease in PR was correlated with neither delta p-GH (N: r = 0.082, DM-NR: r = -0.400, DM-HR: r = 0.242) or integral of GH (N: r = 0.191, DM-NR: r = 0.382, DM-HR: r = 0.162). The fractional excretion of sodium (FENa) decreased in N (p < 0.01), increased in DM-NR (p < 0.05) and did not change in DM-HR. The changes of FENa were not correlated with those of PRA and PAC.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Altered responses of heart rate, renal sodium handling and plasma growth hormone to clonidine in type II diabetic patients]. 133 89

In infant rats short-term administration of the alpha 2-adrenoceptor agonist, clonidine (CLO), induces refractoriness to the growth hormone (GH)-releasing effect of an acute CLO challenge. CLO reportedly stimulates GH release via increased release of GH-releasing hormone (GHRH) from the hypothalamus. Based on these premises, in this study we investigated the possibility that repeated CLO administration may induce down-regulation of hypothalamic alpha 2-adrenoceptors, involved in GH control, thus prohibiting the GH-releasing effect of the drug. alpha 2-Adrenoceptor binding was determined in different brain regions of 10-day-old rats pretreated for 5 days with CLO (150 micrograms/kg, b.i.d.) and killed 14 h after last CLO administration. [3H]p-Aminoclonidine [( 3H]PAC) was used as the specific ligand of alpha 2-adrenoceptors. Treatment with CLO decreased by about 30% the maximum number of binding sites (Bmax) in areas of the mediobasal hypothalamus (MBH) involved in the stimulatory control of GH secretion, i.e. nucleus periventricularis arcuatus, nucleus ventromedialis hypothalami and nucleus lateralis hypothalami. Reduction of Bmax for [3H]PAC binding was observed also in the nucleus periventricularis hypothalami, an area involved in the inhibitory control of GH secretion and, among extrahypothalamic areas, only in the cortex piriformis. In no brain areas was the affinity constant (Kd) for [3H]PAC binding significantly changed after CLO pretreatment. Binding studies performed with a specific ligand of alpha 1-adrenoceptors, [3H]prazosin, showed that the effect of CLO was specific since no changes in the Bmax or Kd were present in either hypothalamic or extrahypothalamic regions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Down-regulation of alpha 2-adrenoceptors involved in growth hormone control in the hypothalamus of infant rats receiving short-term clonidine administration. 216 45

Neurotensin (NT), a tridecapeptide originally isolated from bovine hypothalamus, has numerous actions on endocrine functions. Since intravenous injection of NT in the rat stimulated the release of growth hormone (GH) among several pituitary hormones, the aim of our study was to investigate in humans the effects of GH injection on NT plasma levels. Plasma samples were obtained from 13 children with growth delay (7 boys and 6 girls; age range 5 years 1 month-14 years 1 month; mean +/- SE 10 years 9 months +/- 7 months) to evaluate NT and GH values before treatment and 4, 12 and 24 h after a subcutaneous rhGH injection (0.15 IU/kg). Plasma was extracted on a SEP-PAC C18 column and NT was eluted with propanol. NT concentrations were measured by a specific RIA and expressed as fmol/ml plasma. GH (ng/ml) and somatomedin C (SMC; U/ml) were evaluated by RIA using commercial kits. Free fatty acids (FFA; mEq/l) were measured using a colorimetric peroxidase technique. Before GH administration, NT levels were 7.19 +/- 1.01 fmol/ml. A significant increase in NT values was found 4 h (36.5 +/- 9.62, p < 0.001), 12 h (40.85 +/- 6.64, p < 0.001) and 24 h (19.5 +/- 3.48, p < 0.05) after GH injection. This increase was significantly correlated with the circulating GH levels 4 h after GH administration and with the circulating SMC levels 24 h after GH administration. No correlation was found between NT and FFA values.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of growth hormone administration on neurotensin release in children with growth delay. 799 19

This study describes a double-transgenic model in which monoclonal CD8 F5 T cells are chronically exposed to self Ag (nucleoprotein) in the periphery, but are not affected during thymic development. Chronic exposure of CD8 T cells to their cognate Ag rendered them unable to proliferate or produce cytokines in response to antigenic stimulation in vitro. However, the cells still retained some killer function in vivo and continuously eliminated APC expressing high levels of Ag. In addition, when crossed with mice expressing Ag in the anterior pituitary gland (triple-transgenic mice), F5 T cells migrated to this site and killed growth hormone producing somatotrophs. The anergic state was reversible upon transfer into Ag-free recipients, resulting in full recovery of in vitro responsiveness to Ag. Anergic CD8 T cells express higher levels of CD5, a negative regulator of T cell signaling, whereas after transfer and residence in Ag-free hosts, CD5 levels returned to normal. This suggests that up-regulation of negative T cell regulators in peripheral T cells exposed to chronic stimulation by Ag may prevent full functionality and thus avoid overt autoreactivity.
 ...
PMID:Chronic exposure to low levels of antigen in the periphery causes reversible functional impairment correlating with changes in CD5 levels in monoclonal CD8 T cells. 1287 16

To understand the role of growth hormone-releasing hormone (GHRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) and to examine the functional significance of the co-expression of GHRH and PACAP in fish, their receptors were characterized in zebrafish. Three cDNAs encoding the PAC(1) receptor, the VPAC(1) receptor, and the partial GHRH receptor were identified from zebrafish. Functional expression of the PAC(1) and VPAC(1) receptors revealed that both are potently coupled to the adenylyl cyclase pathway, but only the PAC(1) receptor is coupled to the phospholipase C pathway. Transcripts for all three receptors were widely distributed, often in an overlapping pattern in the adult zebrafish. Also, one splice variant of the partial GHRH receptor and three splice variants of the PAC(1) receptor were identified from adult zebrafish. The long GHRH receptor transcript contained a 27 amino acid insert in transmembrane domain 5 encoding a premature stop codon leading to a truncated receptor protein. For the PAC(1) receptor, two of the splice variants corresponded to the hop1 and hop2 variants characterized in mammals. The third splice variant identified from the gill encoded a novel 107 bp insert containing a premature stop codon. Therefore, PACAP and GHRH have widespread, overlapping target sites suggesting a coordinated role for these hormones in evolution.
 ...
PMID:Characterization of four receptor cDNAs: PAC1, VPAC1, a novel PAC1 and a partial GHRH in zebrafish. 1571 35

Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic hormone that is involved in numerous physiologic functions. The present study examines the presence and the functional significance of PACAP and its receptor in the brain and astrocytes of tilapia (Oreochromis mossambicus). This is the first demonstration of the full-length nucleotide sequence of tPACAP gene in tilapia pituitary, brain, and cultured astrocytes. Two cDNA variants of the growth hormone-releasing hormone (GHRH)-PACAP gene were identified in tilapia pituitary, brain, and cultured astrocytes as a result of exon skipping with a long form (271 bp) encoding both tPACAP(38) and tGHRH and a short form (166 bp) encoding only tPACAP(38). The short form was found to be more abundant in astrocytes. Addition of ovine PACAP(38) (1 nM) to cultured astrocytes significantly stimulated the expression of tPACAP(38) at 4 hrs, but the effect dropped after 8 hrs of treatment. By contrast, the expression of PACAP type I receptor (PAC(1)-R) mRNA in the astrocytes was not responsive to PACAP(38) treatment. The tPACAP(38) expression also was activated by the cAMP analog, dibutyryl-cAMP, in a dose-dependent manner. Adding high salinity (170 mM NaCl, 500 mOsm/kg osmolarity) to cultured medium substantially increased astroglial tPACAP(38) expression over 4 hrs to a level that was maintained for 16 hrs. This observation was not found when mannitol (270 mM) was supplemented as an osmolarity-enhancing agent (500 mOsm/ kg). Taken together, tPACAP expression in tilapia astrocytes was well regulated by exogenous PACAP, cAMP, and salinity and might be involved in the adaptation to high salinity when the fish is in a seawater environment.
 ...
PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates the expression of PACAP in cultured tilapia astrocytes. 1725 34

Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a role in mediating growth hormone and gonadotropin release in the teleost pituitary. In the present study, we examined the immunohistochemical relationship between PACAP nerve fibers and prolactin (PRL)- and somatolactin (SL)-producing cells in the goldfish pituitary. Nerve fibers with PACAP-like immunoreactivity (PACAP-LI) were identified in the neurohypophysis in close proximity to cells containing PRL-LI or SL-LI. Several cells with PRL-LI or SL-LI showed PACAP receptor (PAC(1)R)-LI. The cell immunoblot assay method was used to examine the effect of PACAP on PRL and SL release from dispersed goldfish pituitary cells. Treatment with PACAP increased the immunoblot area for PRL- and SL-LI from individual pituitary cells in a dose-dependent manner. The effect of PACAP on the expression of mRNAs for PRL and SL in cultured pituitary cells was also tested. Semiquantitative analysis revealed that the expression of SL mRNA, but not PRL mRNA, was increased significantly by the treatment with PACAP. The effect of PACAP on intracellular calcium mobilization in isolated pituitary cells was also investigated using confocal laser-scanning microscopy. The amplitude of Ca(2+) mobilization in individual cells showing PRL- or SL-LI was increased significantly following exposure of cells to PACAP. These results indicate that PACAP can potentially function as a hypophysiotropic factor mediating PRL and SL release in the goldfish pituitary.
 ...
PMID:Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on prolactin and somatolactin release from the goldfish pituitary in vitro. 1792 Jul 7

Somatolactin (SL), the latest member of the growth hormone/prolactin family, is a novel pituitary hormone with diverse functions. However, the signal transduction mechanisms responsible for SL expression are still largely unknown. Using grass carp as an animal model, we examined the direct effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on SL gene expression at the pituitary level. In primary cultures of grass carp pituitary cells, SLalpha and SLbeta mRNA levels could be elevated by PACAP via activation of PAC-I receptors. With the use of a pharmacological approach, the AC/cAMP/PKA and PLC/inositol 1,4,5-trisphosphate (IP(3))/PKC pathways and subsequent activation of the Ca(2+)/calmodulin (CaM)/CaMK-II cascades were shown to be involved in PACAP-induced SLalpha mRNA expression. Apparently, the downstream Ca(2+)/CaM-dependent cascades were triggered by extracellular Ca(2+) ([Ca(2+)](e)) entry via L-type voltage-sensitive Ca(2+) channels (VSCC) and Ca(2+) release from IP(3)-sensitive intracellular Ca(2+) stores. In addition, the VSCC component could be activated by cAMP/PKA- and PLC/PKC-dependent mechanisms. Similar postreceptor signaling cascades were also observed for PACAP-induced SLbeta mRNA expression, except that [Ca(2+)](e) entry through VSCC, PKC coupling to PLC, and subsequent activation of CaMK-II were not involved. These findings, taken together, provide evidence for the first time that PACAP can induce SLalpha and SLbeta gene expression in fish model via PAC-I receptors through differential coupling to overlapping and yet distinct signaling pathways.
 ...
PMID:Grass carp somatolactin: II. Pharmacological study on postreceptor signaling mechanisms for PACAP-induced somatolactin-alpha and -beta gene expression. 1852 21

Somatolactin (SL), the latest member of the growth hormone/prolactin family, is a novel pituitary hormone with diverse functions. At present, SL can be identified only in fish but not in tetrapods and its regulation at the pituitary level has not been fully characterized. Using grass carp as a model, we examined the direct effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on SL secretion and synthesis at the pituitary cell level. As a first step, the structural identity of grass carp SL, SLalpha and SLbeta, was established by 5'/3'-rapid amplification of cDNA ends. These two SL isoforms are single-copy genes and are expressed in two separate populations of pituitary cells located in the pars intermedia. In the carp pituitary, PACAP nerve fibers were detected in the nerve tracts of the neurohypophysis and extended into the vicinity of pituitary cells forming the pars intermedia. In primary cultures of grass carp pituitary cells, PACAP was effective in stimulating SL release, cellular SL content, and total SL production. The increase in SL production also occurred with parallel rises in SLalpha and SLbeta mRNA levels. With the use of a combination of molecular and pharmacological approaches, PACAP-induced SL release and SL gene expression were shown to be mediated by pituitary PAC-I receptors. These findings, as a whole, suggest that PACAP may serve as a hypophysiotropic factor in fish stimulating SL secretion and synthesis at the pituitary level. Apparently, PACAP-induced SL production is mediated by upregulation of SLalpha and SLbeta gene expression through activation of PAC-I receptors.
 ...
PMID:Grass carp somatolactin: I. Evidence for PACAP induction of somatolactin-alpha and -beta gene expression via activation of pituitary PAC-I receptors. 1852 22

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs - PAC(1) , VPAC(1) and VPAC(2) - belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC(1) receptors are selective for PACAP, whereas VPAC(1) and VPAC(2) respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC(2) receptor in susceptibility to schizophrenia and the PAC(1) receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=67).
 ...
PMID:Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. 2228 55


1