Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is unknown what cell type(s) in the gonad of the hermaphroditic snail Lymnaea stagnalis is the target(s) of the two gonadotropic hormones, dorsal body hormone (DBH) and caudo-dorsal cell neuro-hormone (CDCH). It was considered that the hormones might act by activating the adenylate cyclase (AC)-cAMP system in the targets. AC activation was determined histochemically. The CDCH (ovulation hormone) titer can be manipulated in vivo by inducing egg laying experimentally ("clean water stimulus"). The effect of the oocyte growth-stimulating DBH and also that of CDCH was studied in in vitro experiments. Only the follicle cells appeared to possess and AC-cAMP system (experiments with forskolin). This system can be activated by DBH, but not by CDCH. Activation can only be brought about in certain stages of the egg-laying process. In vivo this activation was apparent from 30-45 min until 2-3 hr after ovulation, i.e., until 0-1 hr after egg mass deposition. In vitro activation was possible 0-30 min after ovulation. Activation was only obvious in certain stages of oogenesis (not in follicle cells of younger oocyte stages). The results indicate that it is the follicle cells that are the targets for DBH. The possible role of the follicle cells is discussed. The question of what are the targets of CDCH remains unsolved. Apparently this hormone does not act via AC-cAMP, but via another second messenger.
Gen Comp Endocrinol 1986 Aug
PMID:Enzyme cytochemical evidence for the activation of adenylate cyclase in the follicle cells of vitellogenic oocytes by the dorsal body hormone in the snail Lymnaea stagnalis. 378 Dec 31

The multistep fractioning of the protein components from cultural filtrate of B. anthracis grown on casaminoacids containing medium was done. The scheme for preliminary purification of a toxin complex of B. anthracis against low and high molecular mass contaminants has been elaborated and includes ultrafiltration, gel chromatography in ultragel AcA-202 and TSK-gel toyopal HW-55. Biological activities of the complex,toxicity for laboratory animals and adenylate cyclase activity characteristic of B. anthracis toxin, are shown to remain intact in course of preliminary purification. Molecular masses of protein subunits from the fraction containing anthracis toxin activity reach 85-90 kD, 0.3-0.5 mg of toxin complex protein is yielded from 1 l of B. anthracis cultural filtrate.
Mol Gen Mikrobiol Virusol 1985 Dec
PMID:[The use of gel chromatography for the isolation of biologically active toxin complex from Bacillus anthrax]. 393 72

The structure of avian parathyroid hormone (PTH) is only partially known, therefore studies of the avian renal responses to PTH have been conducted using bovine parathyroid extract (bPTE), synthetic human PTH (h(1-34)PTH), and synthetic bovine PTH (b(1-34)PTH). In vitro studies indicate that these peptides may have quite different chick kidney receptor binding affinities and adenylate cyclase activation potencies. In the present study, the in vivo renal responses to bPTE, b(1-34)PTH, and h(1-34)PTH have been compared in immature domestic fowl. The following parameters were evaluated: glomerular filtration rates; renal plasma flow rates; urine pH; and fractional excretion of sodium, potassium, chloride, calcium, magnesium, and inorganic phosphate. Overall, the different hormonal peptides elicited qualitatively similar responses: they all were phosphaturic, natriuretic, diuretic, hypomagnesiuric, hypocalciuric, and kaliuretic. This is the first study to show an effect of PTH on renal magnesium transport in avian species. Quantitative comparisons make it clear that bPTE is more natriuretic and diuretic, but less phosphaturic than either b(1-34)PTH or h(1-34)PTH. A temporal dissociation of the phosphaturic response from the other mineral and electrolyte responses suggests that the phosphaturic response is mediated by a separate mechanism.
Gen Comp Endocrinol 1985 Mar
PMID:Comparisons of avian renal responses to bovine parathyroid extract, synthetic bovine (1-34) parathyroid hormone, and synthetic human (1-34) parathyroid hormone. 398 27

In the present study effects of a new local anaesthetics, pentacaine (trans-2-pyrolidinocyclohexylester of 3-pentyloxyphenylcarbamic acid), and of some chemically related compounds on rat hepatic adenylate cyclase activity were studied under various experimental conditions. As compared with tetracaine, the local anaesthetics tested showed stronger inhibitory effects, regardless of the type of stimulating agents used to activate adenylate cyclase. The most potent effect was observed with pentacaine. Its inhibitory effects on glucagon, guanylylimidodiphosphate (Gpp/NH/p), sodium fluoride or forskolin stimulated activity suggest that it may directly act on the catalytic unit of adenylate cyclase. The same conclusion can be drawn based on its inhibitory effects on adenylate cyclase, regardless ATP concentrations used as the enzyme substrate, and on octylpyranoside solubilized enzyme activated by preincubation of the enzyme preparation with Gpp/NH/p. Structure-activity studies have suggested that the pentacaine molecule as a whole and none of its parts alone or its analogs are responsible for the inhibitory effect. However, the inhibitory effects of these compounds on the rat adenylate cyclase activity do not correlate with their local anaesthetic properties. The possibility of using adenylate cyclase inhibitors to decrease cyclic AMP production under pathological conditions, like in cholera, known to be due to a high adenylate cyclase activity, is discussed.
Gen Physiol Biophys 1985 Oct
PMID:Inhibitory effects of pentacaine and some related local anaesthetics on rat hepatic adenylate cyclase. 406 40

Freshly prepared duck erythrocytes, incubated either in plasma or an isotonic synthetic medium containing norepinephrine ([K] of both media approximately 2.5 mM), maintain water and electrolyte composition in the steady state (upper steady state) for at least 90 min. If incubated in the synthetic medium without norepinephrine or in plasma to which a beta-adrenergic blocking agent (propranolol) is added, the cells lose both water and electrolyte (predominantly KCl) until a new steady state is reached (lower steady state). Reaccumulation of water and electrolyte from isotonic solutions toward the upper steady-state levels requires the addition of norepinephrine and KCl. Reaccumulation is maximal when the concentration of K and norepinephrine in the medium is 15 mM and 10(-7)M, respectively. Dibutyryl cyclic-AMP (10(-2)M) mimics norepinephrine in lower steady-state cells. Although an analogous effect in upper steady-state cells was not established with certainty, it is proposed that the catecholamine-induced net changes in water and electrolyte movement in duck erythrocytes are a consequence of stimulation of the activity of a membrane-bound adenyl cyclase system.
J Gen Physiol 1971 Jun
PMID:The effect of norepinephrine and dibutyryl cyclic adenosine monophosphate on cation transport in duck erythrocytes. 432 71

Serotonin and dopamine, both likely transmitter substances in Aplysia, stimulated formation of adenosine-3',5' monophosphate (cAMP) in ganglia, connectives, and identified nerve cell bodies. This widespread distribution suggests that receptors for the response are localized throughout the nervous system, as is adenyl cyclase. Both synthesis of cAMP-(3)H from precursor previously labeled in incubations with adenine-(3)H and total content of cAMP were stimulated up to 15-fold. The acetylcholine analogue carbachol, glutamate, norepinephrine, and histamine were inactive. Full stimulation occurred within 2-4 min of applying serotonin; the extent of the effect was half maximal at 6micro serotonin. Even in the continued presence of serotonin, the increased cAMP diminished with time. When serotonin was removed, tissue remained refractory for 15-20 min; sensitivity returned after 25 min. Serotonin stimulated cAMP after removal of extracellular Na, K, or Cl and in isotonic sucrose, with all extracellular ions removed. Elevating Mg, which blocked the stimulation of cAMP caused by synaptic activity, did not affect the response to serotonin. Thus the response appeared to be independent of transmitter release and of changes in synaptic potentials and current flow. The role of cAMP in neuronal functioning remains to be determined. Conditions which markedly increased cAMP in neurons, however, did not affect the rate of RNA synthesis, nor did they alter the distribution of phosphorylated adenine or uridine nucleotides.
J Gen Physiol 1972 Nov
PMID:Cyclic adenosine monophosphate in the nervous system of Aplysia californica. II. Effect of serotonin and dopamine. 434 40

The interrelationship of several physiological receptors which influence the hydroosmotic response of the toad urinary bladder was studied employing neurohypophyseal peptides, prostaglandin E(1), theophylline, and cyclic nucleotides. The binding property of agonists (pD(2)), synergists (pS(2)), competitive antagonists (pA(2)), and noncompetitive antagonists (pD(2)') was determined after a suitable methodology had been developed. A series of neurohypophyseal peptides was examined in detail for their catalytic activity. It was found that the replacement of the hydroxy radical of the tyrosine residue in oxytocin by a methoxy and then by an ethoxy radical led to a progressive decline in the catalytic activity of the hormone-corresponding to a change from agonist to partial agonist to competitive antagonist. [4-Leucine]-mesotocin behaved as a competitive antagonist of oxytocin. Prostaglandin E(1) (PGE(1)) was found to be a noncompetitive inhibitor of neurohypophyseal peptides and theophylline; whereas the maximal hydroosmotic response of the bladder to [2-O-methyltyrosine]-oxytocin and theophylline was greatly depressed by PGE(1), the response to saturating concentrations of oxytocin was only slightly diminished-a finding which reveals a "receptor reserve" for oxytocin. Saturating concentrations of [2-O-ethyltyrosine]-oxytocin, inactive per se, potentiate theophylline-disclosing a "threshold phenomenon" for the mediation of neurohypophyseal hormone action. It is concluded that neurohypophyseal peptides are capable of producing graded effects on adenyl cyclase both below and above the range of enzyme activity which evokes graded changes in membrane permeability.
J Gen Physiol 1970 Aug
PMID:Threshold and receptor reserve in the action of neurohypophyseal peptides. A study of synergists and antagonists of the hydroosmotic response of the toad urinary bladder. 543 69

1. To study the effects of maternal alcohol ingestion on brain parameters in offspring, rats were given ethanol for drinking (25% w/v) from the time of mating until sacrifice. Controls drank tap water. 2. Alcohol ingestion reduced daily food and liquid consumption but total caloric intake was only slightly diminished. 3. Maternal body weight increased and offspring body weight, size and brain weight were reduced in the animals receiving alcohol. 4. Brain concentrations of tryptophan, tyrosine and GABA were augmented in ethanol treated mothers at 1 day post-partum. 5. Comparison of brain parameters in offspring of alcoholic mothers with those of controls showed that tryptophan and 5HT concentrations were augmented in 4 day old neonates, NA was increased in 21 day fetuses and 1 day old neonates, and adenylate cyclase activity was also greater in the brains of 21 day fetuses and the cerebellums of 4 day old neonates. 6. Neither phosphodiesterase nor cyclic-AMP concentrations differed in offspring of alcoholic and control mothers. 7. Data showed alterations in brain NA and 5HT systems in the offspring of alcoholic mothers.
Gen Pharmacol 1982
PMID:Effects of maternal ethanol ingestion on cerebral neurotransmitters and cyclic-AMP in the rat offspring. 612 83

alpha-Adrenergic receptor function was assessed in platelets from drug-free schizophrenic patients and control subjects. The number of alpha-receptors was similar in platelet membranes from schizophrenic patients and control subjects. In intact platelets from schizophrenic male, but not female, patients, prostaglandin E1 (PGE1)-stimulated cyclic adenosine monophosphate (cAMP) level was less than in control subjects. This defect may be due, at least in part, to decreased adenylate cyclase activity. In platelet lysates from schizophrenic patients, but not from normal control subjects, adenylate cyclase activity was diminished and PGE1-stimulated adenylate cyclase activity could be restored partially by the addition of guanosine triphosphate. Treatment with neuroleptic drugs or lithium carbonate did not change alpha-receptor number or cAMP production in platelets from schizophrenic patients, but high doses of propranolol hydrochloride increased cAMP production without affecting the number of alpha-receptors. If the production of cAMP in neurons is similar to that in platelets, diminished cAMP production may be associated with a vulnerability to schizophrenia.
Arch Gen Psychiatry 1983 Mar
PMID:alpha-Adrenergic receptor function in schizophrenia. Receptor number, cyclic adenosine monophosphate production, adenylate cyclase activity, and effect of drugs. 613 56

The contractile system of rat cardiac muscle that has been made hyperpermeable by soaking the tissue in EGTA (McClellan and Winegrad. 1978. J. Gen. Physiol. 72:737-764) can be probed directly with Ca buffer from the bathing solution without significant interference from either sarcoplasmic reticulum or mitochondria on the Ca concentration. Changes in Ca-activated force are due therefore to changes in the properties of the contractile system itself and not to regulation of Ca concentration. The addition of cAMP, cGMP, and GTP, guanylyl imidodiphosphate (GMP-PNP), or epinephrine to the bath does not alter maximum Ca-activated force, but when these drugs are added with 1% nonionic detergent to the bath, contractility increases by as much as 180%. An inhibitor of phosphodiesterase must be present for the inotropic effect of cAMP but not cGMP, GTP, GMP-PNP, or epinephrine. The inotropic response to cAMP is independent of the Ca sensitivity of the contractile system, but guanine nucleotides enhance contractility only when Ca sensitivity is not high. The inotropic effect of epinephrine is inhibited to a large extent by cGMP but not by GMP-PNP. These data can be explained by a model in which contractility is enhanced by a cAMP-regulated phosphorylation that can be controlled through the beta-receptor adenylate cyclase complex in the sarcolemma. The regulation involves two reactions, one a phosphorylation and a second that occurs in the presence of detergent. Phosphorylation of neither the myosin light chain nor the inhibitory subunit of troponin appears to be involved in this mechanism for regulating contractility.
J Gen Physiol 1980 Mar
PMID:Cyclic nucleotide regulation of the contractile proteins in mammalian cardiac muscle. 624 20


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