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)

Intradermal injection of Clostridium welchii type-D epsilon toxin increased the permeability of blood vessels in guinea-pig skin to Evans blue dye by a mechanism not dependent on the release of histamine. The toxin was also found to raise the plasma concentration of cyclic adenosine 3', 5'-monophosphate in mice. It is concluded that epsilon toxin is an enterotoxin capable of causing widespread damage, after binding to receptor sites on the surface of certain cells, through a mechanism mediated by an adenyl cyclase-cAMP system.
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PMID:Further studies on the mode of action of Clostridium welchii type-D epsilon toxin. 7 53

1. Rat livers were dissociated into their constituent cells by perfusion through the portal vein with a medium containing collagenase, and hepatocytes separated from non-parenchymal cells. 2. It is shown that the procedure described by Wisher & Evans [(1975) Biochem. J. 146, 375-388] for preparation of plasma membranes from liver tissue when applied to isolated hepatocytes also yielded subfractions of similar morphology and marker-enzyme distribution. 3. Thus the distribution of alkaline phosphodiesterase, 5'-nucleotidase and the basal and glucagon-stimulated adenylate cyclase among two 'light' vesicular and one 'heavy' junction-containing plasma-membrane subfractions paralleled that reported for tissue-derived plasma-membrane subfractions. 4. Increased recoveries and specific activities of plasma-membrane marker enzymes were obtained when soya-bean trypsin inhibitor was included in the collagenase-containing perfusion media used to dissociate the liver. 5. Polyacrylamide-gel-electrophoretic analysis of the corresponding plasma-membrane subfractions prepared from liver tissue and isolated hepatocytes were generally similar. 6. The results indicate that the functional polarity of the hepatocyte's plasma membrane is retained after tissue dissociation. The damage occurring to plasma-membrane ectoenzymes by the collagenase-perfusion procedure is discussed.
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PMID:Preparation of plasma-membrane subfractions from isolated rat hepatocytes. 88 Feb 46

Previous studies suggest that circulating levels of vasopressin (AVP) influence the responsiveness of the kidney to AVP. To determine how changes in renal AVP receptors and adenylate cyclase (AC) contribute to such altered responsiveness, we analyzed AVP receptors and AVP-sensitive AC in kidneys from Sprague-Dawley, Long-Evans and homozygous Brattleboro rats. In autoradiographic studies, the distribution of [3H]AVP binding sites was similar in all groups, corresponding to the location of AVP-sensitive AC: collecting ducts greater than outer medullary collecting ducts greater than medullary thick ascending limb greater than cortical collecting ducts. No differences in AVP receptor affinity or content were observed in kidney medullary membranes from Sprague-Dawley, Long-Evans or Brattleboro rats (KD = 0.8, 0.9, and 0.7 nM; Bmax = 116 +/- 9, 95 +/- 11 and 98 +/- 6 fmol/mg). Basal and AVP-stimulated AC activities were lower in kidney membranes from Brattleboro rats compared with Sprague-Dawley and Long-Evans animals (basal = 28 +/- 4, 40 +/- 4 and 38 +/- 3 pmol cAMP/mg/min; EDmax = 57 +/- 5, 80 +/- 7 and 71 +/- 2 pmol cAMP/mg/min) with no change in ED50. In 48-hour water-deprived Sprague-Dawley rats, AVP receptors were decreased from 116 +/- 9 to 58 +/- 2 fmol/mg, suggesting that AVP receptors are down-regulated by elevated AVP blood levels. The absence of changes in basal or AVP-stimulated AC in dehydrated rats indicates that receptor-AC coupling is normal and that maximum AC activation can occur with partial receptor occupancy. The data also indicate that impaired renal responsiveness to AVP in Brattleboro rats is not due to down-regulation of AVP receptors.
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PMID:Physiologic regulation and distribution of the renal vasopressin receptor. 253 25

The effects of streptozotocin-induced diabetes on the retinal dopaminergic system have been examined in Long-Evans (pigmented) rats. Tyrosine hydroxylase activity was significantly decreased while dopamine-stimulated adenylate cyclase was increased in 2-month-diabetic rats. The observed increase in dopamine-stimulated adenylate cyclase activity in diabetic retinae may be related to neurotransmitter receptor changes because postreceptor activation of adenylate cyclase by guanylyl imidodiphosphate was not altered.
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PMID:Dopamine-stimulated adenylate cyclase and tyrosine hydroxylase in diabetic rat retina. 286 Sep 52

Treatment of Sprague-Dawley rats for 9 days with 15 micrograms/kg of tri-iodo-thyronine, 50 micrograms/kg of thyroxine (T4) or 500 micrograms/kg of thyrotropin-releasing hormone decreased the number of beta receptors in cerebral cortex as measured by dihydroalprenolol binding. The dissociation constants of dihydroalprenolol (3.5 nM) were not altered by the treatment. Only tri-iodo-thyronine and T4 administration resulted in a concomitant reduction of norepinephrine (NE) elicited cyclic AMP formation in cerebral cortical slices. This process required at least a 7-day treatment period and was dose-dependent. Application of 1 microgram of T4 per kg for 9 days significantly diminished the NE responsivity of the cyclic AMP synthesizing system. Dose-response curves with NE indicate a reduction of the maximal response after T4 treatment with no change in ED50. An almost additive interaction between the effects of T4 and a low dose (3 mg/kg) of the tricyclic antidepressant imipramine was observed. Striking differences in the response of the adrenoceptor coupled adenylate cyclase to a 9-day T4 treatment were found when different rat strains, i.e., Fischer F-344, Long-Evans, Wistar and Sprague-Dawley were used. The hyperthyroid state of the animals was ascertained by measurements of plasma levels of tri-iodo-thyronine and T4. Down-regulation of NE sensitive adenylate cyclase by T4 treatment required intact synaptic structures because denervation by i.c.v. injection of 6-hydroxydopamine abolished the effect of T4 treatment. This is indicative of a postsynaptic localization of the down-regulated cyclic AMP generating system. The data stress the importance of the neuroendocrine system for adrenoceptor regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic thyroxine treatment of rats down-regulates the noradrenergic cyclic AMP generating system in cerebral cortex. 298 86

At 4 h after the intraperitoneal administration of kainic acid in a dose of 12 mg/kg, Evans blue extravasation was observed preferentially in the thalamus, accompanied by increases in the water and sodium contents and by a decrease in the potassium content. Subcutaneous pretreatment with a histamine H2-receptor blocking agent, ranitidine, in a dose of 5 mg/kg given 2 h before and at the time of kainic acid injection, partially decreased the edema formation in the thalamus. It is assumed that repetitive discharges evoked by the kainic acid result in the thalamus in an excessive release of histamine from internal (mast cell and neuronal) sources and that this leads to the activation of H2-receptor-coupled adenylate cyclase in the brain microvessels and to the induction of brain edema.
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PMID:Histamine H2-receptors participate in the formation of brain edema induced by kainic acid in rat thalamus. 364 81

From the above, it doesn't seem too rash now to elevate octopamine to the status of a neuroregulator in the invertebrates. To encapsulate, octopamine occurs in high concentration in many higher invertebrates and is found in specific octopaminergic neurons from which it is released upon stimulation. It then interacts with specific receptors, some of which at least, are linked to adenylate cyclase. The action of octopamine is then terminated by re-uptake or by N-acetylation (or a combination of these functions). It is fair to say we know as much about octopamine and its role as a neuromodulator in vertebrates as we do about noradrenaline in vertebrates-only our ignorance isn't as well documented. But where does octopamine fit into the scheme of Barchas et al. (1978)? We can agree that it is a neuroregulator but is it a neurotransmitter or a neuroregulator? Turning to the three well characterized octopaminergic systems, these all seem to be neuromodulatory in nature. Clearly the octopaminergic neurons in the lobster which release octopamine into the haemohymph fall into the neuromodulator class. In the case of the octopaminergic neurons in the adult firefly lantern, octopamine released from these neurons appears to interact with a specific adenylase cyclase-linked receptor and this leads to a response, the flash of the lantern. This therefore appears to be a situation where octopamine is a neurotransmitter, not dependent on other transmitters for actions (Nathanson, 1979). In the system of octopaminergic neurons which originate in the DUM neurons and innervate skeletal muscle, octopamine again appears to be a neuromodulator, altering the response of the muscle to another neurotransmitter (O'Shea and Evans, 1979). However, these peripheral octopaminergic system probably form only a small portion of the octopaminergic neurons in arthropods. The role of octopamine in the central nervous system must remain conjectural for the present.
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PMID:Octopamine--after a decade as a putative neuroregulator. 611 46

The diterpene forskolin has been demonstrated to activate adenylate cyclase in many tissues, independently of receptors, guanyl nucleotides or the guanine nucleotide regulatory protein. Rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) have a defect in the synthesis of vasopressin. This absence of vasopressin is reflected by polyuria and a decrease in the urinary excretion of cyclic AMP, which mediates the action of vasopressin in the epithelial cells of the collecting ducts. Treatment of Brattleboro rats or of control Long-Evans rats with forskolin in doses as low as 7 micrograms/animal produced a significant decrease in urine volume. The reduction in urinary volume was associated with a significant increase in the cyclic AMP content of renal medullary tissue. Thus, systemic activation of adenylate cyclase can correct the pathophysiological consequences of the absence of vasopressin.
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PMID:Correction of polyuria by activation of adenylate cyclase in Brattleboro rats. 654 6

1. Regional haemodynamic responses to the homologous peptides, pituitary adenylate cyclase-activating peptide (1-27) (PACAP27) and vasoactive intestinal polypeptide (VIP) were assessed by giving 20 min infusions (1.5-15 nmol kg-1 h-1) in conscious, chronically-instrumented, Long Evans rats. 2. PACAP27 caused dose-dependent depressor and tachycardic effects associated with renal, mesenteric and hindquarters vasodilatations, although only in the latter vascular bed was there a sustained increase in flow. 3. VIP caused dose-dependent depressor and tachycardic effects that were not significantly different from those caused by equimolar doses of PACAP27. However, the hindquarters vasodilator effects of VIP (at 7.5 and 15 nmol kg-1 h-1) were greater than those of PACAP27 (at the same doses), and accompanied by reductions in renal and mesenteric flows and conductances. 4. In the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 11 mumol kg-1 h-1), there was significant inhibition of the hindquarters vasodilator effects of PACAP27 and VIP (at 7.5 and 15 nmol kg-1 h-1). Under these circumstances the renal and mesenteric vasoconstrictor effects of VIP were abolished. 5. The beta 2-adrenoceptor antagonist, ICI 118551 (670 nmol kg-1 bolus, 335 nmol kg-1 h-1 infusion), reduced the matched hindquarters vasodilator responses to PACAP27 (15 nmol kg-1 h-1) and VIP (7.5 nmol kg-1 h-1), and also abolished the renal vasoconstrictor effects of VIP. 6. The AT1-receptor antagonist, losartan potassium (20 mumol kg-1), had no significant effect on the haemodynamic response to PACAP27 (15 nmol kg-1 h-1), but augmented the hypotensive action of VIP (7.5 nmol kg-1 h-1). This influence of losartan was associated with conversion of the renal and mesenteric vasoconstrictor effect of VIP to vasodilatation. 7. Our findings show that similar changes in mean systemic arterial blood pressure in response to PACAP27 and VIP conceal substantial differences in their regional haemodynamic actions. Although the hindquarters vasodilator effects of both peptides involve NO- and Beta2-adrenoceptor-mediated mechanisms,it appears that activation of the renin-angiotensin system contributes significantly to the haemodynamic effects of VIP, but not to those of PACAP27.
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PMID:Regional haemodynamic responses to pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide in conscious rats. 791 21

As previously reported by this laboratory, an endogenous factor capable of inhibiting the specific binding of the radiolabeled cannabinoid agonist [3H]CP-55940 to its receptor can be released from nerve terminals in response to an influx of Ca++ induced by an ionophore (Evans et al., 1992). In the present report, we provide evidence that the endogenous ligand for the cannabinoid receptor can be released in response to a depolarizing stimulus (75 mM K+) in the presence of extracellular Ca++. K(+)-evoked release was not observed in the absence of extra-cellular Ca++ and was reduced by the specific calcium channel blockers verapamil and omega-conotoxin. The efflux of cannabinoid receptor binding activity is greatest within 2 min of stimulation with the Ca++ ionophore A23187. Within this period of time, the cannabinoid receptor binding activity was enhanced by the presence of a cocktail of peptidase inhibitors. Examination of the contribution of individual inhibitors for enhancing high K(+)-released material revealed a selectivity for captopril and thiorphan. The specificity of the released factor for the cannabinoid receptor was corroborated by its ability to compete with the aminoalkylindole radioligand [3H]WIN-55212 for binding to this receptor. Fractions from a semi-purified sample of the effluent demonstrated binding to the cannabinoid receptor and behaved as agonists in that these fractions could inhibit adenylate cyclase activity in neuroblastoma membrane preparations.
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PMID:Endogenous cannabinoid receptor binding activity released from rat brain slices by depolarization. 813 40


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