Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biological studies of the relationships between the schizoaffective disorders, the affective disorders, and schizophrenia suggest that no simple reductionist model is supported by currently available data. Thus, both affective and schizoaffective patients but not schizophrenics, manifest abnormalities such as decreased platelet serotonin (5-HT) uptake, blunted clonidine-induced increase in serum growth hormone, shortened latency of rapid eye movement (REM) sleep, and increased REM density. However, there are some types of studies which show greater similarity between schizoaffective and schizophrenic patients than between schizoaffectives and affectives--e.g., increased cerebrospinal fluid (CSF) norepinephrine levels, increased platelet 5-HT content, and decreased prostaglandin E1-stimulated adenylate cyclase activity. Other types of studies show abnormalities common to all three groups of psychoses--e.g., eye tracking dysfunction, elevated CSF concentration of gamma-aminobutyric acid, and neuromuscular abnormalities. There are also abnormalities that have been reported to be present in only one type of the psychoses. Although none of these findings have been so unequivocally demonstrated that they can be considered to be firmly established, they do suggest that it is premature to conclude that the schizoaffective disorders are subtypes of the affective disorders. The possibility of a continuum model of the psychiatric psychoses of unknown etiology merits further consideration. Further biological studies of a broad range of psychiatric psychoses with inclusion of the schizoaffective categories appear indicated.
...
PMID:Biological studies of schizoaffective disorders. 642 46

Primary cell cultures were prepared from fetal, neonatal and adult rat pituitaries and evaluated for their ability to secrete growth hormone (GH) in response to growth hormone-releasing factor (GRF). Pituitary cells prepared from fetuses at days 19 and 21 of gestation, neonatal animals at the day of birth (day 0) or the following day (day 1) and peripubertal male rats showed full dose response curves to GRF with maximal GH release when stimulated with 1 X 10(-10) M rat GRF. At this concentration of GRF, the amount of GH released was not different from that elicited by activation of adenylate cyclase with 1 X 10(-5) M forskolin. In contradistinction, a preparation of cells from fetuses at day 18 of gestation did not show the same release of GH when challenged with 1 X 10(-10) M GRF and forskolin (0.057 +/- 0.001, compared to 0.076 +/- 0.003 micrograms/10(5) cells per 4.5 h), although the cells clearly responded to both secretagogues (basal levels of GH, 0.029 +/- 0.002 micrograms/10(5) cells per 4.5 h). While cells prepared from fetuses at day 21 of gestation or from animals after birth released 5-10% of their total cellular GH content, those prepared from 18- and 19-day fetuses released as much as 40% of their total GH suggesting there is a maturation of intracellular GH processing that occurs late in gestation. The results show that, in late pregnancy, the rat fetal pituitary is highly responsive to growth hormone-releasing factor and suggest that this peptide participates in regulating GH levels during the perinatal period.
...
PMID:Ontogeny of the response to growth hormone-releasing factor. 644 42

The effects of rat growth hormone (1 microgram/ml) on the synthesis and release of insulin by isolated rat islets of Langerhans were studied. There was no effect of growth hormone on the release of insulin from freshly isolated islets during 30 min incubation periods. By contrast, islets previously cultured for 16h with growth hormone exhibited at 40% increase in the release of insulin in response to glucose or to glucose and theophylline. These islets also showed specific increases in basal and glucose-stimulated insulin synthesis of 16% and 21% respectively, together with a 22% increase in the basal rate of total protein synthesis. The total insulin content of islets was not affected by culture with growth hormone. The adenylate cyclase activity of islet homogenates was unaffected by the presence of growth hormone during 30 min incubations. When homogenates from islets previously cultured with growth hormone were studied, basal adenylate cyclase activity was unchanged, while fluoride-stimulated adenylate cyclase activity was increased by 37%. It is concluded that growth hormone can directly affect the synthesis and release of insulin in islets of Langerhans, without relation to its metabolic activities in other target organs.
...
PMID:Direct effects of rat growth hormone in rat islets of langerhans in tissues culture. 699 3

Domperidone, a peripheral dopamine (DA) receptor blocker which poorly crosses the blood-brain barrier and which is inactive towards dopamine-sensitive adenylate cyclase, in a dose (100 micrograms/kg) sufficient to increase serum prolactin levels at least 5-fold, decreased the growth hormone (GH) response to the DA receptor agonist, apomorphine HCI (Apo) (0.5 gm s.c.) in each of six normal men examined. The mean GH increment at 30, 45, 60 and 75 min following Apo injection, the mean individual peak increment and the mean individual GH secretion (ng min) was significantly decreased by domperidone pretreatment (p less than 0.005 -p less than 0.002). These results indicate that in man Apo stimulates GH secretion by an effect on DA receptors which are not linked to adenylate cyclase and which are situated at a locus in the hypothalamic-pituitary axis that lies outside the blood-brain barrier.
...
PMID:Effect of domperidone on apomorphine-induced growth hormone secretion in normal men. 710 12

Sulpiride (100 mg IM), an atypical neuroleptic, which does not block dopamine (DA) receptors that are linked to adenylate cyclase, abolished the growth hormone (GH) response to the DA receptor agonist, apomorphine (Apo) HCl (0.5 mg SC) in seven healthy male subjects. These results suggest that Apo increases GH secretion in man by an effect on DA receptors that are not linked to adenylate cyclase.
...
PMID:Effect of sulpiride, an atypical neuroleptic, on apomorphine-induced growth hormone secretion. 713 55

Phospholipid liposomes (PL) are capable of stimulating the activity of dopamine (DA)-sensitive adenylate cyclase in mouse brain, and inducing a modification of the noradrenergic hypothalamic system in rat. Changes of prolactin and growth hormone secretion have been observed in humans given PL. A recent double-blind clinical study suggests that liposomes have a good antidepressive effect in depressive patients. 26 patients with depressive syndrome were included in a double-blind study; 13 patients were treated with clomipramine (CI) + placebo (P), and 13 with CI + PL. The dose of CI was 75 mg orally daily, that of PL was 200 mg by intravenous infusion in 500 ml isotonic saline solution daily. The symptomatology was evaluated on days 0, 7, 14, and 21 using the Hamilton Rating Scale. The results of this controlled trial have shown that both treatment were effective on overall symptomatology but the onset of action of CI + PL was more rapid than CI + P.
...
PMID:Phospholipid liposomes in depression: a double-blind study versus placebo. 718 71

Significant increases in basal, and glucagon and fluoride stimulated adenylate cyclase activity were observed in liver plasma membranes of hypophysectomized rats compared to normal adult and weanling rats. The fluoride stimulated adenylate cyclase activity was 2-3 fold greater in the membranes from hypophysectomized animals while the glucagon stimulated activity was 5-7 fold greater, and the basal activity was approximately double that of membranes from normal adult animals. Administration of growth hormone to hypophysectomized rats by an intramuscular or intravenous route decreased adenylate cyclase activity to levels equivalent to those in normal adult rats. Estradiol and thyroxine replacement did not alter the adenylate cyclase activity of the membranes from hypophysectomized animals. The fluoride or epinephrine stimulated adenylate cyclase activity of rat diaphragm homogenates was not affected by hypophysectomy.
...
PMID:In vivo effect of human growth hormone on hepatic adenylate cyclase activity. 726 31

Previously, we have demonstrated that dopamine (DA) stimulates growth hormone (GH) release from the goldfish pituitary through DA D1 receptors. In the present study, the role of cAMP in DA D1-stimulated GH release was investigated using static incubation of goldfish pituitary cells. The D1 agonist SKF38393 (1 nM-10 microM) induced GH release and cAMP accumulation in a dose-dependent manner with ED50s of 73 +/- 32 and 109 +/- 53 nM, respectively. In contrast, the D2 agonist LY171555 (1 nM-10 microM) was not effective in these regards. The GH-releasing action of SKF38393 was mimicked by the adenylate cyclase activator forskolin (0.1-40 microM) as well as the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 microM-1 mM). Dideoxyforskolin (0.1-40 microM), a derivative of forskolin inactive in stimulating adenylate cyclase, did not affect basal GH secretion. Similar stimulatory effects on GH release were also observed using the membrane-permeant cAMP analogs (10 microM-2 mM), dibutyryl cAMP and 8-bromo cAMP (8Br.cAMP). In the presence of a high dose (1 mM) of Br.cAMP, the ability of SKF38393 (1 nM-10 microM) to stimulate GH release was abolished, suggesting that the GH-releasing actions of cAMP and DA D1 stimulation are mediated through a common signal transduction mechanism. In the present study, the possible involvement of the cAMP-dependent enzyme protein kinase A (PKA) in DA D1-stimulated GH release was also examined. The GH responses to 8Br.cAMP (1 mM) and SKF38393 (1 microM) were blocked by simultaneous treatment with the PKA inhibitor H89 (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Cyclic 3',5'-adenosine monophosphate mediates dopamine D1-stimulated growth hormone release from goldfish pituitary cells. 752 99

The growth hormone (GH)-releasing action of GH-releasing factor (GRF) is known to be cAMP-dependent. However, definitive proof for the involvement of the cAMP-dependent enzyme protein kinase A (PKA) is still lacking. In this study, we characterized the PKA system in purified rat somatotrophs and examined its role in mediating GRF-stimulated GH release under static incubation conditions. PKA enzyme activity was detected only in the cytosolic, but not the particulate fraction of rat somatotrophs. This cytosolic PKA activity exhibited the characteristic cAMP dependence (with ED50 of 0.1 microM), ability to phosphorylate kemptide (a synthetic peptide with a PKA phosphorylation site), and susceptibility to inhibition by the bovine heat-stable PKA inhibitor. GRF treatment (1 pM-1 nM) stimulated the cytosolic PKA activity and GH release from rat somatotrophs in a dose-dependent manner. Time-course studies also demonstrated that activation of cAMP synthesis and PKA activity preceded the GH response to GRF. Stimulation of cytosolic PKA activity in rat somatotrophs by the adenylate cyclase activator forskolin (10 nM-1 microM) and membrane permeant cAMP analog db.cAMP (5 microM-0.5 mM) mimicked the GH-releasing effect of GRF. In contrast, Rp.cAMP, a cAMP antagonist for PKA regulatory subunits, blocked both the cytosolic PKA activity as well as GRF-induced GH release. Similar inhibitions were also observed when an inhibitor for PKA catalytic subunits, H89, was used. Somatostatin (SRIF) (1 nM), the physiological GH-release inhibitor, suppressed the GH response to GRF without affecting the basal or GRF-stimulated PKA activity. SRIF at a higher dose (10 nM) abolished the GH-releasing effect of GRF. In this case, SRIF also induced a small but significant inhibition of GRF-stimulated PKA activity. Taken together, the present study provides direct evidence that PKA enzyme activity is localized only in the cytosol of rat somatotrophs and constitutes an essential component of the signal transduction mechanism for GRF-stimulated GH release. This cytosolic PKA system, however, does not appear to be a major target for the GH-release inhibiting action of SRIF.
...
PMID:Cytosolic protein kinase A mediates the growth hormone (GH)-releasing action of GH-releasing factor in purified rat somatotrophs. 761 38

Somatostatin was discovered for its ability to inhibit growth hormone (GH) secretion. Later, it was found to be widely distributed in other brain regions, in which it fulfills a neuromodulatory role, and in several organs of the gastrointestinal tract where it can act as a paracrine factor or as a true circulating factor. In mammals, two molecules of 14 (somatostatin 14) and 28 (somatostatin 28) amino acids are the only biologically active members of the family. They originate from a single gene which gives rise to a single propeptide alternately cleaved in different tissues. In 1992, a major breakthrough in our understanding of somatostatin functions was made with the cloning of five different receptor genes (sstr1 to sstr5) which belong to the seven transmembrane domain receptor family. Their closer relatives are opioid receptors. In first approximation, the tissular expression of the sstrs matches quite well with the distribution of somatostatin binding sites in the "classical" targets of the peptide ie brain, pituitary pancreatic islets and adrenals. The pharmacology of GH inhibition is very close to sstr2 binding but other actions of somatostatins have not yet been attributed clearly to a single receptor subtype. All clinically relevant agonists tested so far (octreotide, lanreotide and vapreotide) are selective of sstr2 being less potent on sstr3 and inactive for sstr1 and sstr4. Surprisingly, rat sstr5 displays nanomolar affinities for octreotide and vapreotide while these agonists are only active at much higher concentrations on human sstr5. All five receptors can be more or less efficiently coupled to inhibition of adenylate cyclase activity in transfected cell systems.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Molecular pharmacology of somatostatin receptors. 762 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---