Effects of oxytocin and methacholine on cyclic nucleotide levels of rabbit myometrium

1980 ◽  
Vol 58 (3) ◽  
pp. 243-248 ◽  
Author(s):  
N. Schlageter ◽  
R. A. Janis ◽  
R. T. Gualtieri ◽  
O. Hechter
Keyword(s):  
Guanylate Cyclase ◽  
Cyclic Nucleotide ◽  
Phosphodiesterase Inhibitor ◽  
Isometric Tension ◽  
Free Solution ◽  
Cyclic Monophosphate ◽  
Opposing Effects ◽  
Camp Levels ◽  
Camp And Cgmp ◽  
Stimulation Of

The effects of oxytocin and methacholine on cyclic nucleotide levels in estrogen-primed rabbit myometrium were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor. In the absence of MIX, methacholine increased guanosine 3′,5′-cyclic monophosphate (cGMP) levels at a time when contraction was decreasing, but had no influence on adenosine 3′,5′-cyclic monophosphate (cAMP) levels. In contrast, oxytocin did not elevate cGMP, but rapidly increased cAMP levels. MIX (1 mM) increased both cAMP and cGMP levels. Oxytocin or methacholine further increased cGMP, indicating activation of guanylate cyclase. Oxytocin- but not methacholine-induced stimulation of guanylate cyclase was abolished in Ca2+-free solution. Oxytocin increased cAMP over the levels produced by MIX alone, whereas methacholine decreased cAMP below the MIX control values; these effects were insensitive to indomethacin. Tissue levels of cGMP and cAMP did not directly correlate with isometric tension. The results also indicate that both oxytocin and methacholine stimulate guanylate cyclase but have opposing effects on adenylate cyclase of rabbit myometrium.

Prostaglandin E2-histamine in interactions on cAMP, cGMP, and acid production in isolated fundic glands

1982 ◽  
Vol 242 (1) ◽  
pp. G21-G26 ◽  
Author(s):  
R. A. Levine ◽  
K. R. Kohen ◽  
E. H. Schwartzel ◽  
C. E. Ramsay
Keyword(s):  
Prostaglandin E2 ◽  
Acid Secretion ◽  
Acid Production ◽  
Camp Production ◽  
Histamine Stimulation ◽  
Fundic Mucosa ◽  
Biochemical Responses ◽  
Camp Levels ◽  
Camp And Cgmp ◽  
Stimulation Of

Relations among cAMP, cGMP, acid production [measured by the intraglandular accumulation of [14C]aminopyrine (AP)], and prostaglandin E2 (PGE2) activity were studied in isolated glands from rabbit fundic mucosa. AP, cAMP, and cGMP responses to histamine, PGE2, and 3-isobutyl-1-methylxanthine (IMX) were compared with controls. Histamine and PGE2 significantly increased glandular cAMP levels twofold, and histamine and IMX stimulated AP uptake two- to fourfold. PGE2 significantly inhibited both histamine- and IMX-stimulated AP accumulation, but it did not alter basal AP uptake. PGE2 also decreased histamine-stimulated cAMP production but only at a low concentration (10(-7) M). This dose of PGE2 was near to the endogenous PGE2 content found in unstimulated glands (10(-8) M). Intraglandular cGMP levels in unstimulated glands (10(-8) M). Intraglandular cGMP levels were increased by IMX but not by PGE2 or histamine. It is concluded that histamine stimulation of acid secretion is mediated by cAMP, that secretory and biochemical responses to histamine are modulated by PGE2 because PGE2 antagonized histamine-stimulated cAMP and AP uptake, and that the rise in cAMP induced solely by PGE2 appears to be localized within nonparietal cells because PGE2 alone did not stimulate AP accumulation.

Regulation of calcium mobilization and entry in human platelets by endothelium-derived factors

1994 ◽  
Vol 267 (1) ◽  
pp. C236-C244 ◽  
Author(s):  
J. Geiger ◽  
C. Nolte ◽  
U. Walter
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
Human Platelets ◽  
Dependent Protein Kinase ◽  
Rapid Phase ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Dependent Protein ◽  
Camp And Cgmp ◽  
Stimulation Of

Stimulation of Ca2+ mobilization and entry by agonists such as ADP, thrombin, and thromboxane is an early step of platelet activation. Here, we compared the effects of adenosine 3',5'-cyclic monophosphate (cAMP)-elevating prostaglandins, guanosine 3',5'-cyclic monophosphate (cGMP)-elevating nitrovasodilators, membrane-permeant selective activators of cAMP- or cGMP-dependent protein kinases, and physiological endothelium-derived factors on the agonist-evoked Ca2+ mobilization and entry in human platelets. Prostaglandin E1, the prostacyclin analogue Iloprost, the nitric oxide (NO) donor 3-morpholinosydnonimine hydrochloride, and selective activators of cGMP- or cAMP-dependent protein kinase strongly inhibited the agonist-evoked Ca2+ mobilization from intracellular stores and associated late Ca2+ entry but had little effects on the rapid (1st) phase of ADP-evoked Ca2+ entry. During coincubation of platelets with endothelial cells, endothelium-derived factors that were released strongly inhibited platelet agonist-evoked Ca2+ mobilization and only moderately affected the rapid phase of ADP-evoked Ca2+ entry. These effects were partially prevented when endothelial cells were preincubated with cyclooxygenase and/or NO synthase inhibitors. Endothelial cells therefore produce sufficient quantities of labile platelet inhibitors whose effects on the platelet Ca2+ response resemble those observed with selective cAMP- and cGMP-dependent protein kinase activators.

Mechanisms of cyclic nucleotide-induced relaxation in canine tracheal smooth muscle

1995 ◽  
Vol 268 (3) ◽  
pp. L407-L413 ◽  
Author(s):  
I. McGrogan ◽  
S. Lu ◽  
S. Hipworth ◽  
L. Sormaz ◽  
R. Eng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Cyclopiazonic Acid ◽  
Inhibitory Effect ◽  
Beta Agonist ◽  
Cyclic Monophosphate ◽  
Median Effective Concentration ◽  
Camp Levels ◽  
Ca2 Channels

The effects of exogeneous cyclopiazonic acid (CPA, 10 microM), a selective inhibitor of the sarcoplasmic reticulum (SR) Ca2+ adenosinetriphosphatase, on cyclic nucleotide-induced relaxations of canine airway smooth muscle were examined. Strips of tracheal muscle were precontracted with carbachol (50% median effective concentration, 0.1 microM) or with 60 mM KCl. The beta-agonist isoproterenol (ISO, 10 microM) relaxed the tissue by approximately 50%. The relaxation was reduced in the presence of CPA when L-type Ca2+ channels were available but not when these were blocked by 0.1 microM nifedipine. Forskolin (1.0 microM), an adenylate cyclase activator, was less effective at inhibiting the contraction than ISO, and addition of CPA did not block its inhibitory effect as effectively as when ISO was used. Radioimmunoassay indicated that both these agents raised adenosine 3',5'-cyclic monophosphate (cAMP) levels to the same degree. Very little relaxation of the precontracted smooth muscle was elicited by 3 mM 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP), and addition of CPA had no effect. Sodium nitroprusside (100 microM) and 8-bromo-guanosine 3',5'-cyclic monophosphate (10 mM) inhibited contraction to a greater degree than any agent that raised cAMP. These inhibitions were greatly reduced in the presence of CPA when L-type Ca2+ channels were available. We conclude that pumping of Ca2+ into SR plays a major role guanosine 3',5'-cyclic monophosphate-produced but not cAMP-induced relaxation; L-type Ca2+ channels must be available for the relaxant role of Ca2+ pumping into the SR to be expressed; and ISO-induced relaxation may not involve primarily elevation of the cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of adenosine with vasopressin in the inner medullary collecting duct

1990 ◽  
Vol 259 (4) ◽  
pp. F679-F687 ◽  
Author(s):  
Y. Yagil
Keyword(s):  
Pertussis Toxin ◽  
Receptor Agonist ◽  
Collecting Duct ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effects ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct ◽  
Camp Levels ◽  
Dose Dependent ◽  
Stimulation Of

Administration of adenosine (Ado) into rat renal artery induces dose-dependent diuresis that is independent of changes in glomerular filtration rate or renal blood flow, suggesting a direct effect on tubule H2O reabsorption. To test the hypothesis that Ado modulates cellular action of arginine vasopressin (AVP) as a tubular mechanism for the diuretic effect of Ado, interaction of Ado with AVP was studied in primary cell culture of rat inner medullary collecting duct (IMCD) epithelium. Stimulation of cells with 10(-6) M AVP in presence of 0.1 mM Ro 20-1724, a nonmethylxanthine phosphodiesterase inhibitor that has no effect on Ado receptors, increased adenosine 3',5'-cyclic monophosphate (cAMP) levels twofold or more above baseline. Stimulation of cells with the A1 Ado-receptor agonist N6-cyclohexyladenosine (CHA), the A2-receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA), or with the P-site agonist 2',5'-dideoxyadenosine (DDA) significantly inhibited the AVP-stimulated cAMP response. Preincubation with pertussis toxin abolished the inhibitory effects of CHA and NECA, but not of DDA. The data suggest that, in the rat IMCD, Ado modulates AVP action by interfering with its ability to stimulate formation of its second messenger, cAMP. This effect is mediated by the extracellular Ado receptors A1 and A2 and by the intracellular P-site. It occurs by at least two pathways, one sensitive and the other insensitive to pertussis toxin.

CAP2b, a cardioacceleratory peptide, is present in Drosophila and stimulates tubule fluid secretion via cGMP

1995 ◽  
Vol 269 (6) ◽  
pp. R1321-R1326 ◽  
Author(s):  
S. A. Davies ◽  
G. R. Huesmann ◽  
S. H. Maddrell ◽  
M. J. O'Donnell ◽  
N. J. Skaer ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Manduca Sexta ◽  
High Performance ◽  
Fluid Secretion ◽  
Malpighian Tubules ◽  
Cyclic Monophosphate ◽  
Cgmp Signaling ◽  
Camp And Cgmp ◽  
Tubule Fluid ◽  
Stimulation Of

A cardioacceleratory peptide, CAP2b, identified originally in the lepidopteran Manduca sexta, stimulates fluid secretion by Malpighian tubules of the dipteran Drosophila melanogaster. High-performance liquid chromatography analyses of adult D. melanogaster reveal the presence of a CAP2b-like peptide, that coelutes with M. sexta CAP2b and synthetic CAP2b and that has CAP2b-like effects on the M. sexta heart. CAP2b accelerates fluid secretion in tubules stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) but has no effect on tubules stimulated by guanosine 3',5'-cyclic monophosphate (cGMP), implying that it acts through the latter pathway. By contrast, the action of leucokinin is additive to both cAMP and cGMP but not to thapsigargin, suggesting that leucokinin acts by the elevation of intracellular calcium. CAP2b stimulation elevates tubule cGMP levels but not those of cAMP. By contrast, leucokinin has no effect on levels of either cyclic nucleotide. Both CAP2b and cGMP increase transepithelial potential difference, suggesting that stimulation of vacuolar-adenosinetriphosphatase action underlies the corresponding increases in fluid secretion. Overall, the results show that a Drosophila CAP2b-related peptide acts to stimulate fluid secretion by Malpighian tubules through the cGMP-signaling pathway.

Effects of forskolin and cyclic nucleotides on isometric force in rat aorta

1986 ◽  
Vol 250 (3) ◽  
pp. C468-C473 ◽  
Author(s):  
E. G. McMahon ◽  
R. J. Paul
Keyword(s):  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Isometric Force ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Tension Development ◽  
Nucleotide Analogues ◽  
Cyclic Monophosphate ◽  
Contractile System ◽  
Rat Thoracic Aorta

The present study was undertaken to determine the extent to which cyclic nucleotide-induced relaxation in the intact rat aorta is mediated at the level of the contractile system. The relaxant effects of the cyclic nucleotide analogues [8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP)] and forskolin were examined in both the intact vessel and a Triton X-100-skinned preparation of rat thoracic aorta. Relaxation of a norepinephrine-induced contraction was essentially complete 30 min after the addition of 50 microM 8-BrcGMP [% relaxation = 87.2 +/- 4.4% (n = 4)], 100 microM DBcAMP [98.2 +/- 1.2% (n = 4)], and 1 microM forskolin [107.0 +/- 3.3% (n = 5)]. These same doses were ineffective in relaxing precontracted skinned rat aortic rings compared with the relaxation achieved in the intact vessel. The largest relaxation in the skinned aortas was achieved with the addition of 1 microM forskolin [17.4 +/- 1.5% (n = 4)]. The addition of catalytic subunit of cAMP-dependent protein kinase had no effect on isometric tension in the precontracted skinned aorta. Preincubation with the cyclic nucleotide analogues or forskolin in a low-Ca2+ solution (pCa less than 8) was also ineffective in inhibiting subsequent isometric tension development. Our results suggest that only a very small fraction of the relaxation with cyclic nucleotides and forskolin in the intact rat aorta is due to the action of these agents at the level of the contractile system.

Synthesis and vectorial export of cGMP in airway epithelium: expression of soluble and CNP-specific guanylate cyclases

1993 ◽  
Vol 265 (6) ◽  
pp. L598-L605 ◽  
Author(s):  
C. A. Geary ◽  
M. F. Goy ◽  
R. C. Boucher
Keyword(s):  
Natriuretic Peptide ◽  
Guanylate Cyclase ◽  
Cyclic Nucleotide ◽  
Soluble Guanylate Cyclase ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Respiratory Epithelium ◽  
Maximal Velocity ◽  
Lower Efficiency ◽  
Cyclic Monophosphate

Guanosine 5'-cyclic monophosphate (cGMP) is an important modulator of fluid balance in many epithelia. We examined its metabolism in primary cultures of human airway epithelia. Sodium nitroprusside increased cGMP levels 30-fold, suggesting that the respiratory epithelium expresses a soluble guanylate cyclase; however, endogenous nitric oxide production was not detected. cGMP levels could also be increased by C-type natriuretic peptide (CNP), but not by atrial natriuretic peptide, brain natriuretic peptide, or Escherichia coli heat-stable enterotoxin, indicating expression of a CNP-specific membrane-bound guanylate cyclase. The one-half effective concentration for CNP was 40 nM and the maximal velocity was 56.7 pmol cGMP.mg protein-1.h-1. After CNP stimulation, approximately 60% of the total synthesized cGMP was preferentially exported from the polarized epithelial cells across the basolateral membrane by a probenecid-sensitive process. Isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) export revealed a similar export pattern and probenecid sensitivity, although a lower efficiency of export (27% of total cAMP was exported). Consistent with previous reports, export of neither cyclic nucleotide was saturable at the concentrations tested. We conclude that the respiratory epithelium expresses a soluble guanylate cyclase, a CNP-specific receptor, and a novel vectorial cyclic nucleotide export mechanism.

Effect of gonadotrophin-releasing hormone (GnRH) and GnRH agonists upon accumulation of progesterone, cAMP and prostaglandin in isolated preovulatory rat follicles

1982 ◽  
Vol 101 (4) ◽  
pp. 603-610 ◽  
Author(s):  
Torbjörn Hillensjö ◽  
William J. LeMaire ◽  
Martin R. Clark ◽  
Kurt Ahrén
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Fold Increase ◽  
Control Group ◽  
Prostaglandin E ◽  
Gnrh Agonists ◽  
Bicarbonate Buffer ◽  
Preovulatory Follicles ◽  
Camp Levels ◽  
Dose Dependent ◽  
Stimulation Of

Abstract. To study the acute and direct effects of GnRH agonists preovulatory follicles were isolated from PMSG-treated immature rats and incubated for 15–360 min in modified Kreb's bicarbonate buffer. The levels of cAMP, prostaglandin E, and progesterone were analysed in the tissue and/or incubation media. GnRH and two GnRH agonists produced a dose-dependent stimulation of progesterone production with maximal levels 5–6-fold higher than the control group. As compared to LH the magnitude of this effect was small and was detected only after 240–360 min of incubation. GnRH also stimulated prostaglandin E accumulation and this effect was as pronounced as for LH. There were no detectable changes in cAMP levels for any concentration of GnRH when the incubation time varied between 15 and 120 min whether or not a phosphodiesterase inhibitor was present, but after 240 min of incubation a 2-fold incease in cAMP was found. Consistent with previous results, LH caused a pronouced (40–50-fold) increase in follicular cAMP which was already detectable after 15 min of incubation. Indomethacin abolished the rise in prostaglandin E induced either by GnRH or LH but did not affect the response in terms of cAMP or progesterone, and did not affect the stimulation of meiotic maturation of the follicle-enclosed oocytes caused by the hormones. It is concluded that GnRH can exert acute and LH-like stimulatory effects on the preovulatory rat follicle but that the mechanism of GnRH action is different from that of LH.

Stimulation of lipolysis in rat heart myocytes by isoproterenol

1985 ◽  
Vol 248 (2) ◽  
pp. H208-H216 ◽  
Author(s):  
A. Kryski ◽  
K. A. Kenno ◽  
D. L. Severson
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Myocardial Cells ◽  
Cyclic Monophosphate ◽  
Rat Hearts ◽  
Triacylglycerol Content ◽  
Rat Heart Myocytes ◽  
Dose Dependent Increase ◽  
Release Of Glycerol ◽  
Dose Dependent ◽  
Stimulation Of

Calcium-tolerant myocytes were isolated from rat hearts. Isoproterenol produced a dose-dependent increase in glycerol output (lipolysis) that could be blocked by propranolol. The presence of glucose in the incubation medium enhanced the release of glycerol from myocytes but had no effect on the decline in triacylglycerol content. No incorporation of radioactivity from [U-14C]glucose into glycerol could be detected. In incubations with isoproterenol, there was a stoichiometric relationship between the glycerol output and the decrease in triacylglycerol levels. The addition of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine resulted in an increase in the basal glycerol output and an enhancement of the isoproterenol-stimulated lipolytic rate. Forskolin and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate also produced a concentration-dependent stimulation of lipolysis in myocytes. Therefore, lipolysis in isolated myocytes must be regulated by adenosine 3',5'-cyclic monophosphate-dependent mechanisms. These results demonstrate that lipolysis can be observed in myocardial cells and that the lipolytic response to isoproterenol cannot be secondary to a physiological (inotropic) response since these myocyte preparations are quiescent.

Cyclic 3',5'-nucleotide diesterases in dynamics of cAMP and cGMP in rat collecting duct cells

1992 ◽  
Vol 262 (6) ◽  
pp. F957-F964 ◽  
Author(s):  
M. Yamaki ◽  
S. McIntyre ◽  
M. E. Rassier ◽  
J. H. Schwartz ◽  
T. P. Dousa
Keyword(s):  
Ethylene Glycol ◽  
Cell Line ◽  
Collecting Duct ◽  
Tetraacetic Acid ◽  
Free Medium ◽  
Cyclic Monophosphate ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct ◽  
Camp Levels ◽  
Camp And Cgmp

We studied cyclic 3',5'-nucleotide phosphodiesterase (PDE) isozymes and their role in adenosine 3',5'-cyclic monophosphate (cAMP) and cGMP metabolism in a rat inner medullary collecting duct (IMCD) cell line. The homogenized and fractionated IMCD cells of cAMP-PDE and all of cGMP-PDE activity were found in the cytosol. The majority of cytosolic cAMP-PDE (greater than 50%) was isozyme PDE-IV; the Ca(2+)-calmodulin-sensitive PDE-I was present only in cytosol. Preincubation of IMCD cells with PDE-IV inhibitor rolipram markedly (5x) enhanced levels of cAMP both basal and in the presence of [Arg8]vasopressin (AVP). Cilostamide (for PDE-III) or vinpocetine had no effect, whereas PDE-I inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MeoM-IBMX) enhanced AVP-dependent cAMP levels. Exposure of IMCD cells to 2 microM ionomycin decreased both basal and AVP-stimulated cAMP. Depletion of Ca2+ by preincubation of IMCD cells in the Ca(2+)-free medium with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid markedly enhanced the stimulatory response of cAMP to AVP, and addition of 8-MeoM-IBMX further enhanced the AVP response. The levels of cGMP, basal or in response to atriopeptin (ANP), were not affected by PDE-V inhibitor zaprinast, but both inhibitors of PDE-I, 8-MeoM-IBMX and vinpocetine, increased basal cGMP, and 8-MeoM-IBMX also increased cGMP levels enhanced by ANP. The depletion of Ca2+ from IMCD cells alone had no effect on cGMP levels, but effects of 8-MeoM-IBMX and vinpocetine on the ANP-stimulated cGMP levels were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

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