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:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our studies on Madin-Darby canine kidney (MDCK) cells have demonstrated that high-affinity specific muscarinic receptors coupled to the phosphoinositide system are present in these cells. To determine whether muscarinic receptors in MDCK cells are linked negatively to the adenylate cyclase system, we measured the effect of muscarinic agonists and antagonists on vasopressin-, isoproterenol-, and forskolin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation. Vasopressin produced a maximum stimulation of cAMP formation of 13 pmol.10(6) cells-1.2 min-1 at 10(-7) M. Isoproterenol and forskolin stimulated cAMP formation production to 21 pmol.10(6) cells-1.2 min-1 and 64 pmol.10(6) cells-1.10 min-1, respectively, at 10(-4) M. The effects of vasopressin, isoproterenol, and forskolin were blocked by arecoline, a cholinergic agonist, in a concentration-dependent manner. The arecoline response was blocked by treatment of the cells with pertussis toxin. The inhibition by arecoline of forskolin-stimulated cAMP formation was reversed by various muscarinic antagonists in the following order of potency: 4-diphenyl-acetoxy-N-methylpiperidine > p-fluorohexahydrosiladifenidol > pirenzepine > methoctramine. This order of potency of muscarinic antagonists is similar to that observed in our radioligand binding studies and is consistent with the M3 subtype of muscarinic receptors. Our results indicate that muscarinic receptors in MDCK cells are coupled negatively to the adenylate cyclase system via pertussis toxin-sensitive G protein. It is concluded that this intracellular system may at least be partially responsible for the action of cholinergic agonists in these cells and in the kidney.
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PMID:Muscarinic receptors in MDCK cells are coupled to multiple messenger systems. 133 90

There is evidence in the rat that stimulation of renal alpha 2-adrenoceptors modulates vasopressin antidiuretic action and vasopressin-stimulated adenylate cyclase activity. In the present study, we tested the ability of various alpha 2-adrenoceptor agonists to antagonize vasopressin-induced antidiuresis in the conscious hydrated dog and to inhibit vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) generation in rat and dog cortical collecting tubules. Vasopressin infusion (0.01 ng.kg-1.min-1) in five dogs resulted in a decrease in free water clearance from 2.90 +/- 0.42 to -0.34 +/- 0.08 ml/min. The vasopressin receptor antagonist SKF 105494 inhibited this response. Administration of norepinephrine (0.5 microgram.kg-1.min-1) or clonidine (20 micrograms/kg), however, failed to alter the vasopressin-induced antidiuresis. In vitro studies demonstrated that epinephrine caused a dose-dependent reduction in vasopressin-stimulated cAMP levels in cortical collecting tubules from the rat (50% effective concentration 32 nM) but not from the dog. The data indicate that there is a species difference in alpha 2-adrenoceptor modulation of vasopressin action.
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PMID:Modulation of vasopressin antidiuretic action by alpha 2-adrenoceptors is species specific. 165 34

Changes in the intracellular free calcium ([Ca2+]i) of cultured normal human epidermal keratinocytes (NHEK) were investigated in order to determine whether the adenylate cyclase cAMP (AC) system and phospholipase C activating system are involved in increasing [Ca2+]i. NHEK were obtained from neonatal foreskin and grown in serum-free medium (K-GM) supplemented with 2% bovine pituitary extract. [Ca2+]i was measured by fluorescence ratio imaging microscopy using Fura-2 as the indicator. In the case of the AC system, transient increases in [Ca2+]i were observed in response to stimulation with epinephrine, norepinephrine, isoproterenol and salbutamol. Methoxamine, clonidine and dobutamine did not induce any [Ca2+]i increase. The [Ca2+]i increase evoked by epinephrine was inhibited by pretreatment with propranolol, but not by prazosin or yohimbine, indicating that epinephrine-induced [Ca2+]i elevation via beta 2-adrenergic stimulation. Similar changes were observed when NHEK were stimulated with histamine, adenosine, GTP gamma S, forskolin and dibutyryl cAMP respectively. The absence of extracellular Ca2+ had no effect on the epinephrine-induced [Ca2+]i increase. It appears that activated protein kinase A, based on cAMP accumulation via stimulatory GTP binding protein, elicited the release of Ca2+ from intracellular stores. On the other hand, when drugs known to activate phospholipase C in a wide variety of cell types were tested, a transient increase in [Ca2+]i was demonstrated in response to the addition of thrombin, bradykinin and substance P. This reaction was not affected by the presence of EGTA, suggesting that these drugs raise [Ca2+]i via phosphatidylinositol breakdown. Vasopressin, angiotensin II, serotonin and acetylcholine did not induce any increase in [Ca2+]i. On the basis of these studies, it was concluded that NHEK possess the mechanism which increase [Ca2+]i via AC system and phospholipase C activating system. It seems probable that this rise in [Ca2+]i initiates a calcium-dependent cellular response, such as activation of calcium/calmodulin dependent kinase, and subsequently regulates the proliferation and differentiation of human epidermal keratinocytes.
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PMID:[Changes in the intracellular free calcium of cultured human epidermal keratinocytes]. 171 97

Vasopressin binding sites could be clearly demonstrated in the cochlea. Membrane staining was mainly limited to the apical and ciliar membranes of the cochlear and vestibular hair cells, and hence to membranes in which adenylate cyclase activity could not be demonstrated. In addition to V2-vasopressin receptors that mediate hormonal signals by adenylate cyclase activation and cAMP release, in V1-vasopressin-receptors extracellular vasopressin signal is mediated by the breakdown of inositol phosphates and the release of inositol-triphosphates and diacylglycerol. Inositol triphosphates were found to be responsible for the intracellular mobilization of calcium. The localization of vasopressin binding sites at the hair cell membranes, therefore, suggests that vasopressin contributes to the breakdown and release of phospholipid messenger molecules and is thus probably involved in cochlear and vestibular signal transduction.
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PMID:[Hormone receptors in the inner ear]. 252 9

Vasopressin (AVP) plays a key role in maximal urine concentration by stimulating NaCl reabsorption in the medullary thick ascending limbs of Henle (MTAL) and by increasing water permeability in the medullary collecting tubules (MCT). These effects of AVP in MTAL and MCT are mediated by activation of adenylate cyclase. Because effects of high ambient Ca2+ on AVP-sensitive adenosine 3',5'-cyclic monophosphate (cAMP) production are quite different in MTAL and MCT, we examined whether the Ca2+-calmodulin system is involved differently in AVP-sensitive cAMP production in MTAL and MCT of mouse kidney using two dissimilar calmodulin inhibitors, trifluoperazine (TFP) and W-7. TFP and W-7 inhibited AVP-sensitive cAMP production in both nephron segments in a dose-dependent manner with maximal inhibition of both agents being greater than 90%. A half-maximal inhibition by TFP and W-7 was about 45, 100 microM in MTAL and about 40, 40 microM in MCT, respectively. The inhibitory effect of W-5, a chemically similar to W-7 but less potent calmodulin inhibitor, was significantly less than that of W-7 in both nephron segments. TFP and W-7 but not W-5 also inhibited glucagon-sensitive cAMP production in MTAL. W-7 inhibited forskolin-sensitive cAMP production but the inhibition by W-5 was significantly less than that by W-7 in MTAL and MCT. Results suggest that AVP-sensitive cAMP production is MCT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AVP-sensitive cAMP production is dependent on calmodulin in both MTAL and MCT. 284 48

The current study examined the effect of vasopressin on the secretion of phosphatidylcholine, the principal component of pulmonary surfactant, from adult rat alveolar type II pneumocytes in primary culture. Vasopressin stimulated secretion in a time- and dose-dependent manner. At a concentration of 10 nM, vasopressin stimulated release by 6-fold over the basal secretory rate. The concentration producing half the maximal response for vasopressin-induced secretion was 0.4 nM. The stimulation of phosphatidylcholine release by vasopressin was duplicated by the vasopressin fragment, amino acids 4 through 9. [Lys8]vasopressin and the selective vasopressin-2 agonist [deamino-8-D-Arg]vasopressin did not stimulate surfactant secretion effectively. The vasopressin- and fragment-induced secretion was inhibited by the vasopressin-1 receptor antagonist d(CH2)5TDAVP and the protein kinase C inhibitor, tetracaine, but not by the beta-adrenergic antagonist alprenolol. Vasopressin did not activate adenylate cyclase, which suggests that stimulation by vasopressin was independent of cyclic AMP. When vasopressin and isoproterenol were added concomitantly, the effects on phosphatidylcholine secretion were additive. This suggests that these two secretagogues operate via separate mechanisms.
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PMID:Stimulation of surfactant secretion by vasopressin in primary cultures of adult rat type II pneumocytes. 291 96

Mesangial cells respond to vasopressin by contraction and increased prostaglandin production. The purpose of the present study is to characterize vasopressin receptors from these cells. Glomeruli were isolated from rat kidneys and plated for explant growth of mesangial cells. Membranes were prepared from cells grown for 6 wk and tested for their ability to bind [3H]vasopressin (lysine vasopressin). These membranes contained a single class of specific vasopressin binding sites [equilibrium dissociation constant (Kd) = 10 +/- 1 nM, maximal binding capacity (Bmax) = 270 +/- 7 fmol/mg protein for 5 determinations]. Vasopressin induced a dose-dependent (apparent Kact value = 2 nM) accumulation of labeled inositol phosphates in myo[3H]inositol-prelabeled mesangial cells incubated in the presence of 10 mM of Li. Conversely, vasopressin failed to alter the adenylate cyclase activity of mesangial cell membranes. Competition experiments with a series of vasopressin structural analogues that have different degrees of affinity for V2-(renal), V1a- (vascular and hepatic), and V1b- (adenohypophyseal) receptors, indicated that vasopressin receptors from rat glomerular mesangial cells resemble the V1a- receptor subtype.
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PMID:Vasopressin receptors from cultured mesangial cells resemble V1a type. 295 5

Vasopressin is known to mediate its action on the kidney through increasing the concentrations of cyclic AMP. As vasopressin is widely distributed in many extra hypothalamic areas of the brain and can be shown to act centrally, we have investigated the effect of vasopressin on cyclic AMP levels in homogenates of the striatal and locus coeruleus areas. In contrast with the effect obtained on the kidney, vasopressin did not stimulate adenyl cyclase activity in rat brain homogenates in a dose-related manner. The stimulation of cyclic AMP observed with dopamine or noradrenaline in these brain areas and the hippocampus was not affected by the presence of vasopressin. These observations suggest that the action of vasopressin on the brain is not mediated through cyclic AMP.
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PMID:The effects of vasopressin and catecholamines on cyclic AMP in homogenates of rat brain. 298 68

Alpha 2-adrenoceptor agonists attenuate vasopressin-mediated changes in water excretion. The effects on sodium excretion, however, are unclear. We therefore utilized the nonrecirculating isolated perfused rat kidney to study the direct effects of vasopressin and alpha 2-adrenoceptor stimulation on sodium and water excretion in the absence of systemic regulatory systems. The perfusate was a Krebs-Henseleit solution (3.5 g/100 ml Ficoll; 1.0% albumin; 36 degrees C) containing prazosin (30 nM) and propranolol (100 nM) to prevent effects of alpha 1- and beta-adrenoceptor stimulation. Vasopressin (10 microU/ml) produced a significant (P less than 0.05) decrease in both water and sodium excretion. Potassium excretion was not significantly altered. Alpha 2-Adrenoceptor stimulation with l-epinephrine (28 nM) reversed (P less than 0.05) the effects of vasopressin on water and sodium excretion. To confirm that this attenuation was mediated by alpha 2-adrenoceptors, an alpha 2-adrenoceptor antagonist, yohimbine, was administered. Yohimbine (300 nM) blocked the effects of epinephrine on sodium and water excretion (P less than 0.05). The adenosine P-site agonist, SQ 22,536 (100 microM), which mediates its effects through inhibition of adenylate cyclase, produced the same reversal as that of epinephrine on vasopressin-mediated changes. Thus alpha 2-adrenoceptor stimulation antagonized the effects of vasopressin on both water and sodium excretion at the renal level. A corollary to this conclusion is that the function-specific activation of renal adenylate cyclase determines the effect of alpha 2-adrenoceptor stimulation.
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PMID:Alpha 2-adrenoceptor antagonism of vasopressin-induced changes in sodium excretion. 298 46

Vasopressin (ADH) and bradykinin (BK) have been shown to stimulate prostaglandin synthesis in rabbit cortical collecting tubules. We studied ADH and BK effects on osmotic water flow (Lp), Na transport (JNa), and transepithelial voltage (VT). Bath BK but not lumen BK blunted subsequent ADH hydroosmotic responses. This BK effect was prevented by ibuprofen or pertussigen pretreatment and was overcome with exogenous cAMP, suggesting that BK, via prostaglandins, interferes with ADH action on Lp at the cAMP generation step. In contrast, bath BK had no effect on bath-to-lumen (Jb-1Na) or lumen-to-bath (Jl-bNa) Na flux or on VT. As reported by others, ADH lowered Jl-bNa and depolarized VT; however, prostaglandin synthesis inhibitors neither prevented nor reversed these ADH effects. Together, these BK and ADH data do not support regulation of JNa by peptide-stimulated prostaglandins. Moreover, cAMP alone depolarized VT but had no effect on Jl-bNa. Therefore, ADH-induced depolarization of VT may at least partly owe to cAMP effects on VT independent of accompanying changes in JNa. As with Lp, bath BK blunted subsequent ADH effects on VT and, to a lesser extent, Jl-bNa; these BK effects on ADH action were also prevented by ibuprofen or pertussigen pretreatment. The data are consistent with the following model: 1) ADH depolarizes VT and increases Lp via cAMP; 2) ADH decreases JNa via neither cAMP nor prostaglandins; and 3) BK, via prostaglandins, inhibits the actions of ADH on Lp and VT at the inhibitory guanyl-nucleotide regulatory subunit of adenylate cyclase.
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PMID:Mechanism of bradykinin, ADH, and cAMP interaction in rabbit cortical collecting duct. 299 3


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