Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Agonists at alpha 2-adrenoceptors, delta-opioid receptors, and somatostatin receptors were applied to dissociated guinea pig submucous plexus neurons; whole-cell recordings of membrane current showed that they increased the membrane potassium conductance. The conductance affected showed inward rectification, being described by Gag(max)/[1 + exp((V - V0.5)/k)] where V0.5 was about -65 mV and Gag(max) was about 10 nS. The agonists were ineffective when the potassium conductance of the neurons had first been increased by intracellular dialysis with purified guanosine 5'-triphosphate (GTP)-binding proteins (Gi or Go). Agonist actions were prevented by pertussis toxin, applied intracellularly (10-100 ng/ml for several minutes) or extracellularly 1-10 micrograms/ml for 1 hr); in the latter case, the agonist responses were reconstituted by intracellular dialysis with GTP-binding proteins.
 ...
PMID:Potassium conductance increased by noradrenaline, opioids, somatostatin, and G-proteins: whole-cell recording from guinea pig submucous neurons. 197 Jun 5

The effects of CRH and somatostatin (SRIH) on adenylate cyclase (AC) activity, intracellular free calcium concentrations [( Ca2+]i) and in vitro ACTH release were investigated in six human ACTH-secreting pituitary adenomas. In all tumors, CRH induced a marked stimulation (from 69-210% at 10 nM), whereas SRIH caused a definite inhibition (from 29-50% at 100 nM) of membrane AC. When added together, CRH and SRIH caused a purely additive effect on AC. In adenomatous corticotrophs CRH (10 nM) caused [Ca2+]i to rise from 160 +/- 30 nM (mean +/- SD) to 410 +/- 95 nM. CRH-induced transients were biphasic, with an initial peak predominantly due to redistribution from intracellular Ca2+ stores and a secondary phase due to Ca2+ influx. The effects of CRH on [Ca2+]i were totally independent of the stimulation of AC. In fact, cAMP-elevating agents other than CRH did not modify [Ca2+]i. SRIH (100 nM) decreased resting [Ca2+]i (approximately 20-40%) as well as [Ca2+]i rises induced by CRH, arginine vasopressin, or high K+. The effect of SRIH on [Ca2+]i was maintained in presence of high cAMP levels, while was totally abolished after pertussis toxin pretreatment. CRH (10 nM) stimulated ACTH release (from 22.5 +/- 3.5 to 45.0 +/- 8.5 pmol/L) by an extent similar to that elicited by calcium ionophore and forskolin. By contrast, SRIH (0.1 microM) inhibited both basal and CRH-stimulated ACTH release. In conclusion, in human adenomatous corticotrophs SRIH exerts an inhibitory action by reducing both AC activity and, independently, [Ca2+]i. In this way, SRIH can efficiently counteract the stimulatory action of CRH that in these cells involves activation of both cAMP and Ca2+ pathways.
 ...
PMID:Inhibition of basal and corticotropin-releasing hormone-stimulated adenylate cyclase activity and cytosolic Ca2+ levels by somatostatin in human corticotropin-secreting pituitary adenomas. 197 Aug 28

The present study was designed to examine the mode of action of muscarinic agonists on somatostatin secretion in intact gastric tissues, i.e., mucosal segments from the fundus and antrum of rat and the isolated luminally perfused mouse stomach. Methacholine caused similar decreases in somatostatin secretion in segments from the fundus (35 +/- 3%; P less than 0.001) and antrum (35 +/- 2%; P less than 0.001) of rat stomach, and in whole mouse stomach (43 +/- 3%; P less than 0.001). The decrease was the net effect of a dominant inhibition and a lesser stimulation of somatostatin secretion. Pretreatment with the permeant derivative of the acetomethoxy ester form of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM, 15 microM) caused a further decrease in methacholine-induced somatostatin secretion, implying that a stimulatory component existed that was mediated by intracellular calcium. Pretreatment with pertussis toxin (125 ng/ml) for 60 min converted the decrease in somatostatin secretion to an increase above basal levels. The increase induced by pretreatment with pertussis toxin was abolished by additional pretreatment with BAPTA/AM. Procaine (5 mM), which blocks release of calcium from intracellular stores, produced an effect on somatostatin secretion similar to that of BAPTA/AM. The results indicate that 1) methacholine exerts dual inhibitory and stimulatory effects on somatostatin cells of rat and mouse stomach, 2) the dominant effect is inhibitory and sensitive to pertussis toxin, and 3) a concurrent stimulatory effect, mediated by calcium, is unmasked after blockade of the inhibitory effect with pertussis toxin.
 ...
PMID:Functionally distinct muscarinic receptors on gastric somatostatin cells. 197 64

Calcium (Ca2+) ion concentrations that are achieved intracellularly upon membrane depolarization or activation of phospholipase C stimulate adenylate cyclase via calmodulin (CaM) in brain tissue. In the present study, this range of Ca2+ concentrations produced unanticipated inhibitory effects on the plasma membrane adenylate cyclase activity of GH3 cells. Ca2+ concentrations ranging from 0.1 to 0.8 microM exerted an increasing inhibition on enzyme activity, which reached a plateau (35-45% inhibition) at around 1 microM. This inhibitory effect was highly cooperative for Ca2+ ions, but was neither enhanced nor dependent upon the addition of CaM (1 microM) to EGTA-washed membranes. The inhibition was greatly enhanced upon stimulation of the enzyme by vasoactive intestinal peptide (VIP) and/or GTP. Prior exposure of cultured cells to pertussis toxin did not affect the inhibition of plasma membrane adenylate cyclase activity by Ca2+, although in these membranes, hormonal (somatostatin) inhibition was significantly attenuated. Maximally effective concentrations of Ca2+ and somatostatin produced additive inhibitory effects on adenylate cyclase. The addition of phosphodiesterase inhibitors demonstrated that inhibitory effects of Ca2+ were not mediated by Ca2(+)-dependent stimulation of a phosphodiesterase activity. These observations provide a mechanism for the feedback inhibition by elevated intracellular Ca2+ levels on cAMP-facilitated Ca2+ entry into GH3 cells, as well as inhibitory crosstalk between Ca2(+)-mobilizing signals and adenylate cyclase activity.
 ...
PMID:Potent and cooperative feedback inhibition of adenylate cyclase activity by calcium in pituitary-derived GH3 cells. 197 2

Fetal rat dorsal root ganglion neurons (7-8 days in culture) were labeled with [3H]arachidonic acid for 24 h. Stimulation with 10 microM bradykinin (BK) for 30 s resulted in nearly 2-fold increases in levels of radioactive diglyceride and arachidonic acid. A similar result was obtained in the absence of receptor stimulation using the Ca2+ channel agonist BAY K 8644 (10 microM, in the presence of 100 mM potassium chloride) or the Ca2+ ionophore, ionomycin (2.5 microM). If Ca2+ influx was inhibited by adding 3 mM Co2+, a blocker of voltage-sensitive calcium channels, or 2.5 mM EDTA, then BK-stimulated accumulation of both arachidonate and diglyceride was inhibited. These data suggest Ca2+ influx is required for ligand-stimulated accumulation of both arachidonate (a product of diglyceride-lipase or phospholipase A2) and diglyceride (a product of phospholipase C). Two distinct populations of channels may be involved in these reactions since pretreatment with 10 microM nifedipine or 50 microM verapamil (agents which block a subset of voltage-sensitive Ca2+ channels) inhibited BK-stimulated accumulation of arachidonic acid, but did not inhibit diglyceride accumulation. Such functional discrimination appears to have physiological importance; the inhibitory effect of nifedipine and verapamil on BK-stimulated arachidonate release was mimicked by pretreatment with peptides which decrease Ca2+ channel conductance in dorsal root ganglion neurons. The three peptides used were 1 microM neuropeptide Y, 10 microM somatostatin, and 10 microM [N-MePhe3,D-Pro4]-morphiceptin. The effect of neuropeptide Y was blocked by pretreatment with pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modulation by neuropeptides of bradykinin-stimulated second messenger release in dorsal root ganglion neurons. 197 11

Somatostatin inhibited Ca2(+)-induced insulin secretion in permeabilized HIT-T15 cells, albeit with decreased sensitivity relative to intact cells. The inhibitory action required the presence of GTP, whereas GDP could not substitute for GTP. Pertussis-toxin treatment before cell permeabilization abolished the inhibition of secretion. Thus somatostatin, by activating a G-protein, interferes with exocytosis distal to the generation of soluble intracellular messengers.
 ...
PMID:Somatostatin inhibition of Ca2(+)-induced insulin secretion in permeabilized HIT-T15 cells. 197 39

We undertook the present studies to explore the mechanisms by which carbachol inhibits the release of somatostatin-like immunoreactivity (SLI) from D cells. D cells were isolated from canine fundic mucosa by collagenase/EDTA dispersion followed by counterflow elutriation. Carbachol inhibited the release of SLI induced by forskolin, dibutyryl 3':5' cyclic adenosine monophosphate (cAMP), pentagastrin (PG), and 12-0-tetradecanoyl-phorbol-13-acetate in a fashion that could be prevented by pertussis toxin (PT) pretreatment of the D cells. Pertussis toxin also prevented the carbachol-induced inhibition of forskolin-stimulated cAMP generation and PG-stimulated [Ca2+]i mobilization. These data indicate that pertussis toxin sensitive inhibitory guanine nucleotide binding proteins mediate many of carbachol's inhibitory actions on D cells.
 ...
PMID:Mechanisms for muscarinic inhibition of somatostatin release from canine fundic D cells. 197 5

The present studies were performed to characterize the molecular form(s) of somatostatin present in the myenteric plexus and to examine some aspects of the regulatory mechanisms underlying somatostatin release and somatostatin-induced release of acetylcholine from this tissue. We observed the following: (1) Somatostatin-like immunoreactivity (SLI) is present in the myenteric plexus of the guinea pig ileum with somatostatin-14 being the predominant molecular form. (2) Somatostatin-like immunoreactivity is released from isolated myenteric ganglia after stimulation with veratridine or the ganglionic agonist dimethylphenylpiperazinium (DMPP). (3) Calcium entry via the N-type channel appears to play a dominant role in DMPP-induced release of SLI. (4) Somatostatin regulates its own release via a pertussis toxin-sensitive mechanism. (5) Under basal conditions somatostatin-14 stimulates release of acetylcholine in a concentration-dependent manner. (6) Calcium entry via L-type channels is associated with the release of acetylcholine evoked by somatostatin-14.
 ...
PMID:Mechanisms regulating somatostatin release and somatostatin-induced acetylcholine release from the myenteric plexus. 197 7

We have used isolated canine parietal cells to examine the receptor and postreceptor events mediating the inhibitory effects of somatostatin on acid secretion. Somatostatin-14 (S14) and somatostatin-28 (S28) dose dependently inhibited parietal cells stimulated by secretagogues that activate both the adenylate cyclase/cyclic adenosine monophosphate and the inositol phospholipid/protein kinase C cascades. The inhibitory action was mediated via a specific cell surface receptor that consists of a single subunit protein (molecular weight 99,000 d). This receptor recognized S14 and S28 equally well. Somatostatin inhibited parietal cell activity via mechanisms that are both dependent on and independent of a pertussis toxin-sensitive inhibitory guanine nucleotide binding protein.
 ...
PMID:Cellular mechanisms of somatostatin action in the gut. 197 8

The presence of acid in the lumen of the gastric fundus induces release of somatostatin close to the parietal cells; this acts to attenuate acid secretion in response to secretagogues, such as histamine and gastrin. The release of somatostatin within the stomach is further regulated by the activity of cholinergic neurons that inhibit somatostatin release and thus augment acid secretion (disinhibition), and noncholinergic (bombesin) neurons that stimulate somatostatin release and thus attenuate acid secretion. The influence of these neurons and the participation of somatostatin as a paracrine regulator of acid secretion has been probed and validated by the use of selective antagonists (atropine and a bombesin antagonist), somatostatin antiserum and pertussis toxin. Similar mechanisms exist in the distal antral segment of the stomach for the paracrine regulation of gastrin release by somatostatin.
 ...
PMID:Gastric somatostatin: a paracrine regulator of acid secretion. 197 9


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