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

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Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of proteinase inhibitors on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas as compared with those of secretin. Each drug tested was administered i.a. Graded doses of gabexate (1-10 mg) elicited dose-dependent biphasic responses for the secretory rates, bicarbonate concentrations and outputs of pancreatic juice, with maximum effects at approximately 5 mg, but had little effect on the protein concentrations. Camostat, at a high dose of 10 mg, caused significant increases in the secretory rate, bicarbonate concentration and output of pancreatic juice over their basal levels, but had little influence on the protein concentration. Secretin (0.03-0.3 U) usually produced similar to gabexate-induced results (1-5 mg). Both bicarbonate and protein concentrations of the juice obtained with gabexate or camostat were almost the same as those obtained with secretin at a similar secretory rate of pancreatic juice, suggesting the secretory action of gabexate or camostat might be similar to that of secretin. In addition, gabexate (3 mg) and camostat (10 mg) elicited more than the respective additive secretory responses in the presence of i.a. infusion of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (12 micrograms/min) as well as secretin (0.1 U). These results indicate that gabexate and camostat induce water and bicarbonate secretion by acting directly on ductular cells of the dog pancreas, which might be mediated at least partially through cyclic AMP.
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PMID:Gabexate and camostat, synthetic proteinase inhibitors, as direct inducing factors of water and bicarbonate secretion in the isolated and blood-perfused dog pancreas. 168 43

We studied the effect of two peptides, the intracellular Ca2(+)-mobilizing caerulein and the cAMP-mediated secretin, and also the phosphodiesterase inhibitor caffeine on pancreatic secretion and growth in newborn rats. To investigate the secretory response of these substances, and to construct dose-response curves 10-day-old conscious rats were given subcutaneously a single injection of caerulein, secretin, caffeine or the combination of these compounds (caerulein + secretin, caerulein + caffeine). Fifteen min after the injection pancreatic specific trypsin activities were measured in order to estimate depletion of enzymes from the pancreas. To study the pancreatic growth--promoting effect of these substances, newborn rats were treated three times daily for 10 days from the day of birth, using the same experimental groups as described above. Caerulein stimulated both enzyme depletion and pancreatic growth. Secretin stimulated enzyme depletion and increased the trophic effects of caerulein on the pancreas. Caffeine alone or in combination with caerulein did not affect pancreatic enzyme depletion and growth.
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PMID:Secretin potentiates, caffeine does not affect caerulein--stimulated pancreatic enzyme depletion and growth in newborn rats. 169

Previous studies have shown that certain peptides of the secretin-glucagon family stimulate tyrosine hydroxylase activity in sympathetic neurons of the superior cervical ganglion and three of its end organs, i.e., the iris, pineal gland, and submaxillary gland. To determine whether a similar regulation occurs in other sympathetic neurons, the effects of two of these peptides, secretin and vasoactive intestinal peptide, were examined in the right cardiac ventricle of the rat, a tissue innervated primarily by the middle and inferior cervical ganglia. Both peptides stimulated tyrosine hydroxylase activity, measured in situ, in this tissue. In addition, several second messenger systems were investigated as possible mediators of this peptidergic stimulation of tyrosine hydroxylase activity in autonomic end organs. 8-Bromoadenosine 3',5'-cyclic monophosphate and forskolin elevated tyrosine hydroxylase activity in slices of both the right ventricle and the submaxillary gland. 8-Bromoguanosine 3',5'-cyclic monophosphate also stimulated tyrosine hydroxylase activity in both tissues, whereas nitroprusside stimulated activity only in the submaxillary slices. Furthermore, the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine and/or Ro 20-1724 potentiated the stimulation by secretin, as well as the stimulations by forskolin and nitroprusside. Phorbol 12,13-dibutyrate also stimulated tyrosine hydroxylase activity in cardiac and submaxillary slices; however, no potentiation of these effects was seen following addition of either phosphodiesterase inhibitor. These data, taken together with those of previous studies, suggest a role for a cyclic nucleotide, probably adenosine 3',5'-cyclic monophosphate, in the peptidergic stimulation of tyrosine hydroxylase activity in sympathetic nerve terminals.
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PMID:Effects of peptides of the secretin-glucagon family and cyclic nucleotides on tyrosine hydroxylase activity in sympathetic nerve endings. 170 18

Pituitary adenylate cyclase-activating polypeptide (PACAP), a peptide of the glucagon-secretin-vasoactive intestinal polypeptide superfamily, was isolated in pure form from the brain of the European green frog, Rana ridibunda. The primary structure of the peptide indicates that evolutionary pressure to conserve the complete amino acid sequence has been very strong. Frog PACAP comprises 38 amino acid residues and contains only 1 substitution (isoleucine for valine at position 35) compared with human/ovine/rat PACAP. In the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, synthetic ovine PACAP-(1-38) produced a dose-dependent increase in the concentration of cAMP in isolated frog anterior pituitary fragments (ED50 = 2.1 +/- 0.6 x 10(-7) M; mean +/- SE; n = 6). Maximum stimulation (an approximately 8-fold increase in concentration over basal values) was produced by 10(-6) M peptide. The truncated form of PACAP [PACAP-(1-27)] also produced a dose-dependent increase in cAMP in frog anterior pituitary fragments, and the potency of the peptide (ED50 = 5.9 +/- 0.6 x 10(-8) M) was comparable to that of PACAP-(1-38). The data suggest, therefore, that the function as well as the structure of PACAP have been conserved during the evolution of amphibia to mammals.
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PMID:Primary structure of frog pituitary adenylate cyclase-activating polypeptide (PACAP) and effects of ovine PACAP on frog pituitary. 172 95

The effects of the cyclic phosphodiesterase (PDE) inhibitors, rolipram, 3-isobutyl-1-methylxanthine (IBMX), amrinone and zaprinast on pancreatic exocrine secretion were investigated in anesthetized dogs. Rolipram (1-30 nmol), IBMX (44-440 nmol) or zaprinast (1-10 mumol) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but amrinone (up to 53 mumol) did not. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by rolipram and IBMX, but neither was affected by zaprinast. Rolipram elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with rolipram were additive. Rolipram and IBMX, but not zaprinast, increased cyclic AMP concentration but did not affect cyclic GMP concentration. These results suggest that rolipram, IBMX and zaprinast have direct secretory properties on pancreatic exocrine glands of the dog, which may be mediated through the increase of intracellular cyclic AMP concentration, by inhibiting PDE activity. Furthermore, the pancreatic PDE enzyme in the dog pancreas may be mainly a type IV.
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PMID:Effects of the cyclic nucleotide phosphodiesterase inhibitors, rolipram, 3-isobutyl-1-methylxanthine, amrinone and zaprinast, on pancreatic exocrine secretion in dogs. 172 88

Secretin receptors in membranes from the neuroblastoma-glioma hybrid cell line NG108-15 were investigated by 125I-secretin binding and adenylate cyclase activation. On both parameters the corresponding relative potencies of parent peptides were, respectively: secretin greater than helodermin greater than peptide histidine isoleucinamide = vasoactive intestinal peptide. With secretin analogs and secretin fragments, the order of potency for binding was: secretin = [Val5]secretin greater than [Ala2]secretin = [Ala11]secretin greater than [Ala4, Val5] secretin greater than [Ala4]secretin greater than [D-Phe4] secretin greater than [D-Phe2]secretin = secretin (2-27) greater than secretin (3-27) greater than secretin (7-27). Also, on adenylate cyclase, [D-Phe4]secretin, [D-Phe2]secretin, secretin (2-27) and secretin (3-27) were partial agonists while secretin (7-27) was ineffective. The differentiating agent N6,2'-O-dibutyryladenosine 3',5'-monophosphate (1 mM) increased the density of secretin receptors and secretin-stimulated adenylate cyclase activity after a lag period of 4 h. After incubation for 24 h, receptor number and enzyme activity were increased 4- and 3-fold, respectively. These effects were inhibited totally by 1 microgram/ml cycloheximide and halved by 5 micrograms/ml actinomycin D. They were mimicked by 1 mM sodium butyrate but were not reproduced by either 8-bromoadenosine 3',5'-monophosphate or the phosphodiesterase inhibitor rac-4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone.
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PMID:Secretin receptors in the neuroglioma hybrid cell line NG108-15. Characterization and regulation of their expression. 217 30

In guinea pig pancreatic acini rat calcitonin gene-related peptide (CGRP) caused an eightfold increase in amylase release with various phosphodiesterase inhibitors present. Rat CGRP and rat [Tyro]CGRP caused half-maximal effect at 2 nM, and were threefold more potent than human CGRP. CGRP-stimulated amylase release was not inhibited by VIP-(10-28) or secretin-(5-27). CGRP stimulated cAMP and was augmented by phosphodiesterase inhibitors with the order of sensitivity being Ro-20-1724 greater than isobutylmethylxanthine greater than theophylline. CGRP did not increase 45Ca outflux or effect of 125I-VIP binding. CGRP specifically inhibited 125I-CGRP binding. The dose-response curves were broad and each peptide accelerated dissociation of bound 125I-CGRP. Computer analysis demonstrated two classes of CGRP-binding sites. Occupation of a high-affinity class (Kd 20 nM) correlated with stimulation of enzyme secretion and cAMP, and occupation of the low-affinity class (Kd 1 microM) correlated with accelerated dissociation. These studies demonstrate that CGRP interacts with specific pancreatic receptors, CGRP-stimulated cAMP is in a different compartment from that stimulated by other secretagogues, and CGRP differs from other agents that increase cAMP and amylase release in the relationship among receptor occupation, cAMP generation, and enzyme secretion.
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PMID:Mechanism of action of calcitonin gene-related peptide in stimulating pancreatic enzyme secretion. 242 55

Vasoactive intestinal peptide (VIP) was originally isolated from porcine duodenum and considered to be a gut hormone. Recent evidence indicates that it may also be involved in reproductive functions. In this study, a possible action of VIP on steroidogenesis by cultured testicular cells was investigated. Neonatal testicular cells were treated in vitro with hormones for 3 days and medium steroid or cAMP content was measured by radioimmunoassay. Treatment of cultured cells with VIP (10(-9) to 10(-6) M) increased the production of testosterone, progesterone, and pregnenolone in a dose-dependent fashion. Testosterone production in response to 10(-6) M VIP was about 5-10% of that maximally induced by LH. Addition of methyl-isobutyl-xanthine, a phosphodiesterase inhibitor, to the VIP-containing cultures significantly enhanced production of testosterone by 13-fold, of progesterone by 9-fold, and of pregnenolone by 2.5-fold as compared to treatment with VIP alone. Additional experiments also showed a dose-dependent stimulation of cAMP production by VIP. The VIP-related hormones PHM-27, secretin, and glucagon also stimulated progesterone and testosterone production with a potency order (PHM-27 greater than secretin greater than glucagon) consistent with that observed for other VIP receptor-mediated actions. A direct stimulatory effect of VIP on Leydig cells was indicated in studies on steroidogenesis by testicular cells separated on a metrizamide density gradient. In these studies, VIP stimulated androgen production in an LH-responsive subpopulation of testis cells but failed to affect steroid production in non-LH-responsive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasoactive intestinal peptide stimulates androgen biosynthesis by cultured neonatal testicular cells. 243 Aug 45

The effect of secretin on acid and pepsin secretion and gastrin release in the totally isolated vascularly perfused rat stomach was studied. With the phosphodiesterase inhibitor isobutyl methylxanthine (IMX) added to the vascular perfusate, baseline acid secretion was 4.7 +/- 1.1 (mean +/- S.E.M.) mumol/h and baseline pepsin output 1147 +/- 223 micrograms/h. Secretin significantly inhibited acid output to a minimum of 1.4 +/- 0.2 mumol/h at a concentration of 25 pM in the vascular perfusate (P less than 0.01). Pepsin output was not significantly different from baseline at any of the secretin doses tested. Threshold secretin concentration for acid inhibition was 5 pM. IMX stimulated gastrin output from 48 +/- 9 pM in the basal state to 95 +/- 13 pM after IMX (P less than 0.01). Secretin inhibited gastrin release only at the maximal dose of 625 pM, when gastrin concentration in the venous effluent decreased from 93 +/- 19 to 68 +/- 19 pM after secretin. Thus, in the totally isolated vascularly perfused rat stomach secretin in physiological concentrations inhibits acid secretion by a direct action on the acid secretory process and not via gastrin inhibition. The study also suggests that gastrin release at least in part is mediated via increased intracellular cAMP.
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PMID:The effect of secretin on acid and pepsin secretion and gastrin release in the totally isolated vascularly perfused rat stomach. 243 26

Membrane currents were recorded from voltage-clamped Xenopus laevis oocytes, surrounded by their enveloping follicular and epithelial cells. Porcine vasoactive intestinal peptide (VIP) generated a membrane current due to an increase in membrane conductance to K+. The VIP current was mimicked by the adenylate cyclase activator forskolin and was potentiated by phosphodiesterase inhibitors, suggesting that adenosine 3',5'-cyclic monophosphate (cyclic AMP) plays a role in mediating the response. Though resembling the follicle's responses to catecholamines and adenosine in ionic basis and apparent mechanism, the response to VIP was not blocked by catecholaminergic or purinergic antagonists, indicating the presence of a specific VIP receptor in the follicle. Among the VIP related peptides, PHM-27 generated similar but smaller K+ currents and porcine secretin and glucagon neither elicited a response nor blocked that to VIP. After treating follicles with collagenase to remove the epithelial and follicular cells the responses to VIP were either substantially reduced or abolished, suggesting that the VIP receptors and K+ channels are both located in the follicular cells.
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PMID:Membrane currents elicited by porcine vasoactive intestinal peptide (VIP) in follicle-enclosed Xenopus oocytes. 244 88


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