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PubMed1999

PACAP-induced formation of cyclic AMP in the chicken brain: regional variations and the effect of melatonin.

We have studied the effects of pituitary adenylate cyclase-activating polypeptide (PACAP27 and PACAP38) on cyclic AMP formation in chick brain, and the action of melatonin upon the PACAP-evoked effects. PACAP stimulated cyclic AMP production in the hypothalamus>cerebral cortex>pineal gland>optic lobes. In the hypothalamus and cerebral cortex, the rank-order of both PACAP forms and VIP in evoking the cyclic AMP response was: PACAP38 approximately PACAP27>>VIP, suggesting the presence in the tested tissues of PAC1 receptors. Melatonin suppressed (IC50=19.8 nM) the PACAP27 (0.1 microM)-induced cyclic AMP response in the hypothalamus, but not in the cerebral cortex. Melatonin also suppressed the hypothalamal cyclic AMP synthesis stimulated by forskolin, but not that evoked by histamine or isoprenaline. Our observations show that PACAP is capable of potently stimulating cyclic AMP formation in some regions of the chick brain, and suggest that the hypothalamus may be a site for a functional interaction between PACAP and the pineal hormone melatonin.

Animals↗
PubMed1999

Cyclic AMP increases hydroxyindole-O-methyltransferase mRNA levels in the chicken pineal gland, but is not required for circadian rhythmicity of this transcript.

Hydroxyindole-O-methyltransferase (HIOMT) plays an important role as the final enzyme in the synthesis of melatonin. In the chicken pineal gland, HIOMT mRNA concentration exhibits a circadian rhythm with a threefold peak at midday. The present study sought to evaluate the possible role of cyclic AMP in this transcriptional rhythm. In cultured pineal glands from 4-day-old chicks, cyclic AMP analogs and the adenylate cyclase activator, forskolin, increased HIOMT mRNA levels twofold to threefold in a dose-dependent manner. Vasoactive intestinal polypeptide increased HIOMT mRNA levels by 50%. Actinomycin-D chase experiments indicated that cyclic AMP did not affect the stability of HIOMT mRNA, thus providing indirect evidence that the effect of cyclic AMP was exerted at transcriptional level. In cultured pineal glands from 11 days embryos, HIOMT mRNA levels failed to respond to cyclic AMP. However, a daily rhythm of HIOMT mRNA, with an endogenous component in constant darkness was clearly observed at this developmental stage. This observation indicates that cyclic AMP is not required for circadian rhythmicity of HIOMT gene transcription.

Acetylserotonin O-Methyltransferase↗
PubMed2002

Cyclic AMP-independent relaxation mediated by beta3-adrenoceptors on guinea pig gastrointestine.

In this study, we investigated the signal transduction pathway involved in beta(3)-adrenoceptor-mediated relaxations of guinea pig gastric fundus and duodenum. In the presence of beta1- and beta2-adrenoceptor blockade, the potency (pD2 value) of catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline) and beta(3)-adrenoceptor agonists ((R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium (BRL37344) and (+/-)-[4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride ((+/-)-CGP12177A)) to induce relaxation was not affected by the adenylate cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ-22,536, 100 microM). Catecholamines induced an elevation of cyclic AMP and SQ-22,536 significantly abolished the responses of gastric fundus. However, cyclic AMP levels were unaltered by the beta3-adrenoceptor agonists in gastric fundus and by the five agonists in duodenum. Furthermore, the relaxant responses to catecholamines and to beta3-adrenoceptor agonists were unaffected by the cyclic AMP-dependent protein kinase inhibitor, N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H-89, 10 microM) in gastric fundus. These results suggest that beta3-adrenoceptor-induced relaxation is mediated through both cyclic AMP-dependent and cyclic AMP-independent pathways in gastric fundus and through a cyclic AMP-independent pathway in duodenum.

Adenine↗
PubMedDate not supplied

Panic disorder patients have reduced cyclic AMP in platelets.

Little is known about the intracellular mechanisms involved in the pathophysiology of panic disorder (PD). Abnormalities in the cyclic AMP system have been described in several psychiatric disorders but there are no studies in panic patients. We evaluated not only the levels of platelet cyclic AMP, but also cyclic GMP and nitric oxide synthase (NOS) activity in patients with PD at baseline and after treatment with clomipramine and in healthy volunteers. Platelet cyclic AMP was determined by enzymeimmunoassay, cyclic GMP by radioimmunoassay and NOS activity by the conversion of (3)H-arginine to (3)H-citruline in 17 PD patients before treatment with clomipramine, after remission of panic attacks and in 22 healthy volunteers. Average baseline cyclic AMP of PD patients was lower than after remission of panic attacks (P<0.005) and lower than in healthy volunteers (P<0.005). Average cyclic AMP after remission of panic attacks was not significantly different than in healthy volunteers. There were no significant differences in cyclic GMP and NOS analysis. Our results suggest that PD patients without treatment have lower platelets cyclic AMP levels than healthy volunteers and that this decrease may be corrected by clomipramine.

Adolescent↗
PubMed1988

Cyclic AMP: a second messenger of the newly characterized AVP-like insect diuretic hormone, the migratory locust diuretic hormone.

An AVP-like neurohormone was extracted from suboesophageal and thoracic ganglia of Locusta migtatoria, isolated, characterized and synthesized. It functions as a diuretic hormone in this species by enhancing the excretion of urine from the MT. It appears to act by increasing cyclic AMP; synthetic AVP-like IDH increases cyclic AMP of the MT in vitro in a time-dependant, dose-dependant and very specific manner. 8-BR-cyclic AMP, an analog of cyclic AMP known to enter the cells, mimics the diuretic action of the AVP-like IDH. Furthermore, the combined actions of forskolin (the activator of the adenylate cyclase) and IBMX (the inhibitor of the phosphodiestherase activity) increase both MT cyclic AMP level and excretion of the primary urine. We conclude from these results that cyclic AMP is a second messenger of the AVO-like IDH.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Mutation of glycine 49 to valine in the alpha subunit of GS results in the constitutive elevation of cyclic AMP synthesis.

The G-protein GS couples hormone-activated receptors with adenylyl cyclase and stimulates increased cyclic AMP synthesis. Transient expression in COS-1 cells of cDNAs coding for the GS alpha-subunit (alpha S) or alpha S cDNAs having single amino acid mutations Gly49----Val or Gly225----Thr elevated cyclic AMP levels, resulting in the activation of cyclic AMP dependent protein kinase. Stable expression in Chinese hamster ovary cells of alpha S Val49 cDNA resulted in a small constitutive elevation of cyclic AMP that was sufficient to persistently activate cyclic AMP dependent protein kinase activity 1.5-2-fold over basal activity. Stable expression of wild-type alpha S or alpha S Thr225 in Chinese hamster ovary cells was less effective in sustaining elevated cyclic AMP synthesis and kinase activation compared to alpha SVal49.

Animals↗
PubMed1981

Role of cyclic AMP in a serotonin-evoked slow inward current in snail neurones.

One model of synaptic transmission suggests that transmitters modify postsynaptic permeability through the intermediary of cyclic AMP. Thus, serotonin (5-hydroxytryptamine) evokes in molluscan neurones a decrease in a voltage-dependent K+ conductance which in turn generates a slow inward current when studied in steady voltage-clamp conditions. The serotonin-induced increase of the plateau phase of the spike of an Aplysia sensory neurone can be mimicked by both intracellularly injected cyclic AMP and extracellularly applied phosphodiesterase inhibitors, suggesting that cyclic AMP mediates the effect. We have tested whether a similar mechanism could account for the serotonin slow inward current in identified snail neurones and have found that the intracellular injection of cyclic AMP, but not of cyclic GMP or 5'-AMP, evokes a slow inward current showing similar voltage dependence, inversion potential and ionic properties to the serotonin slow inward current. Phosphodiesterase inhibitors at low concentrations (1-20 microM) potentiate the serotonin slow inward current and at higher concentrations evoke by themselves an inward current, partially or totally occluding the serotonin and cyclic AMP currents. Finally, we have found that in homogenates of pooled identified snail neurones serotonin stimulates the adenylate cyclase, increasing its activity by 50-100%.

Animals↗
PubMedDate not supplied

Patch- and voltage-clamp analysis of cyclic AMP-stimulated inward current underlying neurone bursting.

The second messenger cyclic AMP has been variously reported to affect the electrical activity of different neurones by decreasing outward potassium current, increasing outward current and increasing inward current. The recently developed patch clamp method of recording single ionic channels allows direct measurement of the action of cyclic AMP on membrane conductances. Using the patch clamp, the closure of potassium channels by cyclic AMP has previously been documented on the single channel level. We report here that in a bursting molluscan neurone, intracellular iontophoresis of cyclic AMP under voltage clamp elicits an inward current of maximal amplitude in the pacemaker voltage region. Patch-clamp analysis reveals inward channels whose opening frequency is augmented by cyclic AMP stimulation and whose activity accompanies burst episodes. Channel opening frequency is significantly increased by depolarization of the whole soma, but not by focal depolarization of the patch; this may reflect the action of another second messenger that acts in concert with cyclic AMP to confer voltage sensitivity.

Animals↗
PubMed1989

Epinephrine and dDAVP administration in patients with congenital nephrogenic diabetes insipidus. Evidence for a pre-cyclic AMP V2 receptor defective mechanism.

We recently showed that the administration of the antidiuretic V2 specific agonist, 1-desamino[8-D-arginine]vasopressin (dDAVP), to seven male patients with congenital nephrogenic diabetes insipidus (CNDI) did not cause a decrease in blood pressure nor an increase in plasma renin activity or factor VIIIc or von Willebrand factor release. In normal subjects, plasma renin activity, coagulation factors and plasma cyclic AMP are stimulated not only by dDAVP but also by the administration of epinephrine. In the present study, we measured tissue plasminogen activator (activity and antigenicity), von Willebrand factor multimers, plasma and urinary cyclic AMP concentrations following dDAVP or epinephrine administration. We infused epinephrine into three male patients with CNDI. Factor VIIIc and tissue plasminogen activator augmented by 75 to 100% and von Willebrand Factor multimers were increased; plasma renin activity and plasma cyclic AMP concentration increased by 200%. None of these values changed when the same subjects as well as eleven other male patients with CNDI received dDAVP. Furthermore, dDAVP administration increased plasma cyclic AMP concentrations in normal subjects, but not in 14 male patients with CNDI. These results demonstrate the specificity of the extrarenal V2 receptor defect expressed in our patients. The lack of a plasma cyclic AMP response to the administration of dDAVP would suggest an altered pre-cyclic AMP stimulation mechanism.

Adult↗
PubMed1999

Effects of the adenylyl cyclase inhibitor SQ22536 on iloprost-induced vasorelaxation and cyclic AMP elevation in isolated guinea-pig aorta.

The stable prostacyclin analogue, iloprost relaxes a variety of blood vessels and increases cyclic AMP, although the relationship between adenosine 3': 5'-cyclic monophosphate (cyclic AMP) and vasorelaxation remains unclear. We therefore investigated the effect of the adenylyl cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) on iloprost-mediated relaxation and cyclic AMP elevation in endothelium-denuded aortic strips. Iloprost (1-1000 nM) caused a concentration-dependent inhibition of phenylephrine (1-6 microM) contractions, the responses being unaffected by pre-incubation with SQ22536 (100 microM) for 30 min. In other experiments 60 nM iloprost caused a 64% inhibition of phenylephrine contractions concomitant with a 3 fold rise in cyclic AMP. SQ22536 completely abolished the iloprost-induced elevation in cyclic AMP while having no significant effect on relaxation. Our results therefore strongly suggest that cyclic AMP-independent pathways are responsible for the vasorelaxant effects of iloprost in guinea-pig aorta.

Adenine↗
PubMed1999

Pharmacological modulation of secondary mediator systems--cyclic AMP and cyclic GMP--on inflammatory hyperalgesia.

1. The objective of the present paper was to evaluate the relevance of neuronal balance of cyclic AMP and cyclic GMP concentration for functional regulation of nociceptor sensitivity during inflammation. 2. Injection of PGE2 (10-100 ng paw-1) evoked a dose-dependent hyperalgesic effect which was mediated via a cyclic AMP-activated protein kinase (PKA) inasmuch as hyperalgesia was blocked by the PKA inhibitor H89. 3. The PDE4 inhibitor rolipram and RP73401, but not PDE3 and PDE5 inhibitors potentiated the hyperalgesic effects of PGE2. The hyperalgesic effect of dopamine was also enhanced by rolipram. Moreover, rolipram significantly potentiated hyperalgesia induced by carrageenan, bradykinin, TNF alpha, IL-1 beta, IL-6 and IL-8. This suggests that neuronal cyclic AMP mediates the prostanoid and sympathetic components of mechanical hyperalgesia. Moreover, in the neuron cyclic AMP is mainly metabolized by PDE4. 4. To examine the role of the NO/cyclic GMP pathway in modulating mechanical hyperalgesia, we tested the effects of the soluble guanylate cyclase inhibitor, ODQ. This substance counteracts the inhibitory effects of the NO donor, SNAP, on the hyperalgesia induced by PGE2. 5. The ODQ potentiated hyperalgesia induced by carrageenan, bradykinin, TNF alpha, IL-1 beta, IL-6 and IL-8. In contrast, ODQ had no significant effect on the hyperalgesia induced by PGE2 and dopamine. This indicates that the hyperalgesic cytokines may activate soluble guanylate cyclase, which down-regulate the ability of these substances to cause hyperalgesia. This event appears not to be mediated by prostaglandin or dopamine. 6. In conclusion, the results presented in this paper confirm an association between (i) hyperalgesia and elevated levels of cyclic AMP as well as (ii) antinociception and elevated levels of cyclic GMP. The intracellular levels of cyclic AMP that enhance hyperalgesia are controlled by the PDE4 isoform and appear to result in activation of protein kinase A whereas the intracellular levels of cyclic GMP results from activation of a soluble guanylate cyclase.

Animals↗
PubMed2000

Effects of P(1) and P2 receptor antagonists on beta, gamma-methyleneATP- and CGS21680-induced cyclic AMP formation in NG108-15 cells.

1. We have previously shown that ATP increased cyclic AMP in NG108-15 cells, which was inhibited by P(1) receptor antagonist methylxanthines. In the present study, we examined the effects of P(1) and P2 receptor antagonists on cyclic AMP formation induced by beta,gamma-methyleneATP (beta,gamma-MeATP) and CGS21680, an A(2A) adenosine receptor agonist, in NG108-15 cells. 2. beta,gamma-MeATP and CGS21680 increased intracellular cyclic AMP with EC(50) values of 8. 0+/-0.98 microM (n=4) and 42+/-7.5 nM (n=4), respectively. 3. Several P(1) receptor antagonists inhibited both beta,gamma-MeATP- and CGS21680-induced cyclic AMP increase with a similar rank order of potency; ZM241385>CGS15943>XAC>DPCPX. However, the pK(i) values of these antagonists for beta,gamma-MeATP were larger than those for CGS21680. 4. Alloxazine, a P(1) receptor antagonist, and several P2 receptor antagonists (PPADS, iPPADS, reactive blue-2) inhibited beta, gamma-MeATP-induced response, while these antagonists little affected CGS21680-induced one. Suramin was effective only for beta, gamma-MeATP-induced response at 1 mM. 5. 2-chloroadenosine (2CADO) and 2-chloroATP (2ClATP) increased cyclic AMP with similar potencies. The effects of these agonists were both inhibited by ZM241385, but only 2ClATP-induced response was inhibited by PPADS. 6. ATP- and beta, gamma-MeATP-induced responses were little affected by alpha, beta-methyleneADP, a 5'-nucleotidase inhibitor. 7. These results clearly demonstrate that ATP-stimulated cyclic AMP formation can be distinguished from the A(2A) receptor agonist-induced one by using the several P(1) and P2 receptor antagonists.

5'-Nucleotidase↗
PubMed2000

Characteristics of the Ca(2+)-dependent inhibition of cyclic AMP accumulation by histamine and thapsigargin in human U373 MG astrocytoma cells.

1. Histamine, acting on H(1)-receptors, caused a Ca(2+)-dependent inhibition of forskolin- and isoprenaline-induced cyclic AMP accumulation in monolayers of human U373 MG cells (IC(50) 1.3+/-0.3 microM, maximum inhibition 66+/-3%). The inhibition was not reversed by the protein kinase inhibitor K-252A. 2. Thapsigargin also inhibited cyclic AMP accumulation (IC(50) 6.0+/-0.3 nM, maximum inhibition 72+/-1%). In the absence of extracellular Ca(2+) 5 microM thapsigargin caused only a 12+/-2% inhibition of cyclic AMP accumulation. 3. The inhibitory effect of 100 nM thapsigargin on forskolin-stimulated cyclic AMP accumulation was blocked by La(3+) (best-fit maximum inhibition 81+/-4%, IC(50) 125+/-8 nM). In contrast, the inhibitory action of 10 microM histamine was much less sensitive to reversal by 1 microM La(3+) (33+/-5% reversal, compared with 78+/-6% reversal of the inhibition by thapsigargin measured concurrently). However, in the presence of both thapsigargin and histamine the inhibition of cyclic AMP accumulation was reversed by 1 microM La(3+) to the same extent as the inhibition by thapsigargin alone. 4.++Thapsigargin (5 microM)+1 microM La(3+) caused only a 20+/-1% inhibition of histamine-stimulated phosphoinositide hydrolysis. 5. There was no indication from measurement of intracellular Ca(2+) of any persistent La(3+)-insensitive Ca(2+) entry component activated by histamine. 6. The results provide evidence that Ca(2+) entry is required for the inhibition by histamine and thapsigargin of drug-induced cyclic AMP accumulation in U373 MG astrocytoma cells. The differential sensitivity of the inhibitory action of the two agents to block by La(3+) suggests that more than one pathway of Ca(2+) entry is involved.

Adenylyl Cyclase Inhibitors↗
PubMed1980

A peripheral and an intrinsic enzyme constitute the cyclic AMP phosphodiesterase activity of rat liver plasma membranes.

1. Approx. 10% of the rat liver cellular cyclic AMP phosphodiesterase activity was associated with a plasma-membrane fraction. 2. Lineweaver-Burk plots of this activity were clearly non-linear, yielding extrapolated Km values of 0.7 and 60.6 microns. 3. Treatment of these membranes with high-ionic-strength NaCl solutions apparently released 80% of this activity assayed at 0.4 micron-cyclic AMP, and 15% of the activity assayed at 1 mM-cyclic AMP. 4. The high-salt-solubilized enzyme gave a non-linear Lineweaver-Burk plot. 5. The cyclic AMP phosphodiesterase activity of the washed high-salt-treated membranes exhibited a linear Lineweaver-Burk plot, yielding a Km of 60 microns. 6. The high-salt-solubilized enzyme exhibited a single peak of activity upon polyacrylamide-gel electrophoresis, a single peak upon sucrose-density-gradient centrifugation (3.9 S) and decayed as a single exponential upon heat-treatment (half-life 1 min at 55 degrees C). 7. The activity of washed high-salt-treated membranes decayed as a single exponential upon heat-treatment (half-life 42 min at 55 degrees C), and was solubilized in the detergent Triton X-100. 8. Cytosol-derived cyclic AMP phosphodiesterase activity could bind to washed high-salt-treated plasma membranes, but was totally eluted by washing with 1 mM-KHCO3, unlike the high-salt-solubilized enzyme, which required high salt concentrations to elute it. 9. We suggest that the cyclic AMP phosphodiesterase activity of rat liver plasma membranes can be resolved into two components: a single peripheral protein exhibiting apparent negative co-operativity, that is distinct from cytosol forms, and an intrinsic protein exhibiting normal Michaelis kinetics.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Fatty acids reverse the cyclic AMP inhibition of triacylglycerol and phosphatidylcholine synthesis in rat hepatocytes.

The influence of cyclic AMP analogues and fatty acids on glycerolipid biosynthesis in monolayer cultures of rat hepatocytes was investigated. Chlorophenylthio-cyclic AMP and adenosine 3':5'-cyclic phosphorothioate inhibited the rate of triacylglycerol synthesis from [1(3)-3H]glycerol, and phosphatidylcholine synthesis from [Me-3H]-choline. Supplementation of the hepatocytes with palmitate (1 mM) reversed chlorophenylthio-cyclic AMP inhibition of triacylglycerol synthesis. Similarly, cyclic AMP analogue-inhibition of phosphatidylcholine synthesis was abolished when the cells were simultaneously incubated with oleate (3 mM). Reactivation of phosphatidylcholine synthesis in chlorophenylthio-cyclic AMP-supplemented cells with oleate was accompanied by conversion of CTP: phosphocholine cytidylyltransferase into the membrane-bound form, since these cells released the enzyme more slowly after treatment with digitonin. The opposing actions of cyclic AMP and fatty acids are discussed in relation to the regulation of glycerolipid biosynthesis during starvation, diabetes and stress.

Animals↗
PubMed1984

Ca2+-calmodulin-, cyclic AMP- and cyclic GMP-induced phosphorylation of proteins in purified microvillus membranes of rabbit ileum.

Evidence is available to suggest that Ca2+-calmodulin and cyclic nucleotides are involved in the regulation of ion transport in rabbit ileum. Since both Ca2+-calmodulin and cyclic nucleotides exert many of their effects by phosphorylation, the effects of Ca2+-calmodulin and cyclic nucleotides on phosphorylation of purified microvillus membrane from rabbit ileal mucosa were evaluated. Ca2+-calmodulin increased phosphorylation of five microvillus-membrane peptides, with Mr values of 137000, 77000, 58000, 53000 and 50000. The increases in phosphorylation caused by Ca2+-calmodulin were: Mr-137000 peptide, 111 +/- 26%; Mr-77000 peptide, 71 +/- 17%; Mr-58000 peptide, 51 +/- 8%; Mr-53000 peptide, 113 +/- 20%. These increases were maximal at 1 microM-calmodulin and 0.3-0.9 microM free Ca2+; concentrations of Ca2+ causing half-maximal effects on phosphorylation for the different peptides were 0.06-0.12 microM. Cyclic AMP and cyclic GMP increased phosphorylation of two peptides, of Mr 137000 and 85000. The concentrations of cyclic nucleotides giving half-maximal phosphorylation of the Mr-137000 peptide were 0.3 microM-cyclic AMP and 4.6 microM-cyclic GMP, and for the Mr-85000 peptide, 3.9 microM-cyclic AMP and 0.05 microM-cyclic GMP. The maximal increase in phosphorylation of the Mr-137000 peptide was 200% for cyclic AMP and 95% for cyclic GMP, and that of the Mr-85000 peptide was 220% for cyclic AMP and 120% for cyclic GMP. These studies demonstrate the existence of Ca2+-calmodulin-, cyclic AMP- and cyclic GMP-dependent protein kinases and substrate proteins in purified rabbit ileal microvillus membranes and that Ca2+ can regulate phosphorylation of these proteins over the presumed physiological concentration range of cytosol free Ca2+.

Animals↗
PubMed1985

Adenosine potentiates lutropin-stimulated cyclic AMP production and inhibits lutropin-induced desensitization of adenylate cyclase in rat Leydig tumour cells.

The action of adenosine on lutropin (LH)-stimulated cyclic AMP production and LH-induced desensitization of adenylate cyclase in rat Leydig tumour cells was investigated. Adenosine and N6-(phenylisopropyl)adenosine caused a dose-dependent potentiation of LH-stimulated cyclic AMP production at concentrations (0.01-10 microM) which alone did not produce an increase in cyclic AMP production. However, 2-deoxyadenosine had no effect either alone or in combination with LH on cyclic AMP production. The potentiation produced by adenosine was unaffected by concentrations of the specific nucleoside-transport inhibitor dipyridamole, which inhibited [3H]adenosine uptake by up to 90%. The phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine, but not RO-10-1724, inhibited the adenosine-induced potentiation. In the presence of adenosine, the kinetics of LH-stimulated cyclic AMP production were linear with time up to 2h, compared with those with LH alone, which showed a characteristic decrease in rate of cyclic AMP production after the first 15-20 min. Consistent with the altered kinetics, adenosine also inhibited the LH-induced desensitization of adenylate cyclase. These results suggest that adenosine has effects on rat tumour Leydig cells through receptors on the external surface of the plasma membrane. This receptor has characteristics similar to those of the R-type receptors, which have been shown either to stimulate or to inhibit adenylate cyclase. However, the effects of adenosine in the present studies does not involve a direct inhibition or activation of adenylate cyclase, but may involve an as yet undefined receptor-mediated modulation of adenylate cyclase.

Adenosine↗
PubMed1985

Acute change in the cyclic AMP content of rat mammary acini in vitro. Influence of physiological and pharmacological agents.

The cyclic AMP content of acini, freshly prepared from mammary tissue of lactating rats, was measured during incubation in vitro. Neither adrenergic agonists nor cyclic AMP phosphodiesterase inhibitors alone caused a change of more than 2-fold in the basal cyclic AMP content of acini. Together, however, these agents provoked increases of around 20-fold in acini cyclic AMP content. Forskolin caused similar effects. The relative potency of adrenergic agonists in increasing cyclic AMP in acini, together with the ability of selective antagonists to oppose such rises, indicated that beta 2-adrenergic receptors were involved in mediating the effects. Receptor-binding experiments using [3H]dihydroalprenolol and selective beta-antagonists confirmed the predominant presence of beta 2-adrenergic receptors on acini membranes and on membranes prepared from purified mammary secretory epithelial cells. These results elucidate some previous findings [Robson, Clegg & Zammit (1984) Biochem. J. 217, 743-749; Williamson, Munday, Jones, Roberts & Ramsey (1983) Adv. Enzyme Regul. 21, 135-145], questioning the role of cyclic AMP in the regulation of lipogenesis in mammary acini.

Adrenergic Agonists↗