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)

Distal nephron segments are heterogenous with respect to adenylate cyclase responses to stimulation with parathyroid hormone (PTH) or calcitonin (CT). We examined effects of these hormones and of 8-(p-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPTcAMP) on net Ca absorption (Jnet Ca2+, pmol.min-1.mm-1) in rabbit distal nephron segments by in vitro microperfusion technique. We studied three segments, including distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD). PTH (1 nM) in bath significantly increased Jnet Ca2+ from 2.28 +/- 0.35 to 9.44 +/- 1.13 in CNT, but did not affect Jnet Ca2+ in DCT or CCD. CT (1 nM) in bath significantly increased Jnet Ca2+ from 1.58 +/- 0.29 to 4.45 +/- 1.01 in DCT, whereas it did not affect Jnet Ca2+ either in CNT or in CCD. CPTcAMP (30 microM) in bath significantly increased Jnet Ca2+ from 2.29 +/- 0.42 to 3.97 +/- 0.43 in DCT and from 2.43 +/- 0.18 to 5.83 +/- 0.37 in CNT, but it did not affect Jnet Ca2+ in CCD. When Na+ was removed from bathing fluid or when 0.1 mM ouabain was added to bath, Jnet Ca2+ in both DCT and CNT significantly decreased. Furthermore, stimulatory effects of PTH and CT on Ca2+ absorption in the respective segments were abolished under these conditions. These results suggest that PTH and CT increase Ca2+ absorption in CNT and DCT, respectively, through cAMP-mediated mechanisms. Presence of a basolateral Na(+)-Ca2+ exchange process seems to be a prerequisite for effects of these hormones. However, exact intracellular mechanisms remain uncertain.
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PMID:Effects of PTH, calcitonin, and cAMP on calcium transport in rabbit distal nephron segments. 169 36

The present studies were performed to investigate the mechanism whereby alpha 2-adrenergic receptor occupancy inhibits the hydrosmotic action of antidiuretic hormone (ADH) in isolated cortical collecting tubules (CCT). The ADH-ribosyltransferase activity of pertussis toxin (PT) was used to promote covalent modification in CCT Ni, the inhibitory regulatory protein of adenylate cyclase, which presumably mediates the alpha 2-adrenergic inhibition of water flow. Tubules preincubated with PT were studied after the addition of ADH and then after the superimposition of clonidine. In these studies, the inhibition of Jv (water absorption, nl X mm-1 X min-1) and Pf (water permeability coefficient, cm/s), by the addition of 10(-4) M clonidine to the bath, was attenuated by PT in a concentration-dependent manner. Reversal of the inhibitory action of clonidine was accomplished with a concentration of 1.0 micrograms/ml PT. To further elucidate the molecular basis of Ni-mediated transduction of the alpha 2-adrenergic signal, ADP-ribosylation studies were undertaken in membrane preparations of dissected CCT segments. PT ADP ribosylated a 40,000 Mr peptide which was proportional to the amount of membrane protein added. Furthermore, pretreatment of CCT during dissection with 0.5 micrograms/ml PT dramatically decreased the susceptibility of the subunit of Ni (alpha i) to be subsequently ADP ribosylated by PT, when compared with CCT preparations not previously treated with PT. Cholera toxin ADP ribosylated a 42,000 Mr peptide from CCT membranes and PT pretreatment did not interfere with the reaction. We conclude that CCT segments have both the pertussis and cholera toxin substrates and the effect of clonidine to attenuate ADH action is mediated through Ni.
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PMID:Prevention of alpha 2-adrenergic inhibition on ADH action by pertussis toxin in rabbit CCT. 288 51

Binding of [125I]glucagon was measured in microdissected pieces of tubules from the rat nephron. Specific glucagon binding sites were found only in nephron segments containing a glucagon-sensitive adenylate cyclase activity. At 7.5 nM labelled hormone, higher levels of specific binding (16-27 X 10(-18) mol mm-1) were found in the thick ascending limb of the Henle's loop and in the distal convoluted tubule and lower binding levels (2-5 X 10(-18) mol mm-1) in the collecting tubule whereas specific binding could not be detected in the proximal tubule and in the thin segments of the Henle's loop. In the medullary thick ascending limb, Scatchard analysis of specific [125I]glucagon binding indicated an apparent equilibrium dissociation constant of 2.4 nM. The stereospecificity of binding sites in medullary thick ascending limbs and medullary collecting tubules, was assessed by competition experiments using unlabelled glucagon, enteroglucagon and unrelated hormones (vasopressin, calcitonin, parathyroid hormone and insulin); in both segments, glucagon was more active than enteroglucagon in displacing labelled glucagon from its tubular binding sites, whereas all other hormones tested were inactive. These results indicate that tubule binding sites might be the physiological receptors for glucagon involved in adenylate cyclase activation.
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PMID:Glucagon receptors along the nephron: [125I]glucagon binding in rat tubules. 299 91

Hypothyroidism has been demonstrated to be associated with an impaired concentrating capacity and specific morphological changes in the thick ascending limbs. This study was performed to evaluate the cellular action of arginine vasopressin (AVP) in the isolated renal tubules from control (C) and hypothyroid (HT) rats. Hypothyroidism was induced by feeding aminotriazole for 4 wk. Urinary volume was higher in HT rats (C 13.5 +/- 0.9, HT 17.7 +/- 0.9 ml/24 h, P less than 0.005) and urinary osmolality was lower in HT rats (C 1,707 +/- 49, HT 1,229 +/- 35 mosmol/kgH2O, P less than 0.001). Plasma AVP levels were significantly higher in HT rats (C 1.93 +/- 0.59, HT 4.12 +2- 0.62 pg/ml, P less than 0.05), thus documenting AVP resistance. The adenylate cyclase response to AVP (10(-6) M) was significantly lower (P less than 0.02) in the medullary thick ascending limb of Henle's loop (mTALH) in HT (14.3 +/- 2.4 to 41.7 +/- 5.8 fm X 30 min-1 X mm-1, P less than 0.001) than in mTALH in C rats (14.4 +/- 2.8 to 110.1 +/- 24.9 fm X 30 min-1 X mm-1, P less than 0.001). In contrast, the adenylate cyclase response to AVP was not significantly different in collecting tubules of cortex, outer medulla, and inner medulla from C and HT rats, although a slight decrease in response to AVP was observed in cortical and outer medullary collecting tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular action of arginine vasopressin in the isolated renal tubules of hypothyroid rats. 303 19

Two groups of Sprague-Dawley rats, Harlan (H) and Charles River (CR), were discovered in that the medullary thick ascending limb (MAL) had a profoundly different adenylate cyclase response to arginine vasopressin (AVP). Using these two groups of rats, we studied the correlation between AVP action on the MAL and maximal urinary concentration. AVP (10(-6) M) significantly stimulated adenylate cyclase in MAL of H rats (7.4 +/- 0.9 to 43.8 +/- 4.6 fmol cAMP formed X 30 min-1 X mm-1, P less than 0.001) but not in CR rats (10.3 +/- 1.4 to 12.7 +/- 2.0 fmol cAMP formed X 30 min-1 X mm-1, NS). In contrast, AVP significantly stimulated adenylate cyclase of cortical, outer and inner medullary collecting tubules from both H and CR rats. Glucagon (10(-6) M) significantly stimulated adenylate cyclase of MAL from both H and CR rats. After 48 h of fluid deprivation, urinary osmolality was significantly higher (P less than 0.001) in the H (4,504 +/- 399 mosmol/kg H2O, n = 14) than CR (2,840 +/- 176 mosmol/kg H2O, n = rats. This observation was not attributable to differences in creatinine clearance (CR, 1.30 +/- 0.24; H, 1.24 +/- 0.03 ml/min, NS, n = 4) or plasma AVP (CR, 12.75 +/- 1.44; H, 12.38 +/- 1.17 pg/ml, NS, n = 6) levels. These results therefore suggest that the action of AVP on the MAL, in addition to the effect on collecting tubules, is involved in maximal urinary concentration in rats.
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PMID:Role of arginine vasopressin in medullary thick ascending limb on maximal urinary concentration. 374 Feb 73

Effects on Ca2+ transport of parathyroid hormone (PTH) and N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (DB-cAMP) were examined in the rabbit distal nephron segments including the cortical thick ascending limb of Henle's loop (CAL), the connecting tubule (CNT) and the cortical collecting tubule (CCT) by the in vitro perfusion technique. When PTH (10(-8) mol . l-1) was added to the bath, efflux of Ca2+ (pmol . mm-1 . min-1) was increased from 6.29 +/- 1.46 to 7.96 +/- 1.66 (P less than 0.02) in the CAL, and from 8.55 +/- 1.30 to 13.73 +/- 1.24 (P less than 0.001) in the CNT, respectively, without changes in influx of Ca2+. The effect of PTH on Ca2+ transport in the CAL, however, was abolished when phosphate concentration in the medium was reduced from 3.0 to 1.0 mmol . l-1. When DB-cAMP (10(-3) mol . l-1) was added to the bath, efflux of Ca2+ was also increased from 7.01 +/- 0.83 to 9.40 +/- 0.82 (P less than 0.05) in the CAL, and from 13.11 +/- 0.89 to 19.74 +/- 0.52 (P less than 0.005) in the CNT, respectively. By contrast, neither PTH nor DB-cAMP affected efflux of Ca2+ in the CCT. PTH did not affected the transepithelial voltage either in the CAL or in the CNT. But in the CNT, DB-cAMP decreased the voltage from -14.1 to -9.4 mV. The response of adenylate cyclase activity to PTH in the collagenase treated isolated nephron segments was also examined. Significant increases in adenylase cyclase activity were observed in the CAL as well as in the CNT with 10(-6) mol . l-1 PTH. These data indicate that PTH stimulates Ca2+ transport across the CNT probably via activation of the adenylate cyclase-cyclic AMP system. The hormone may also stimulate Ca2+ transport across the CAL in a special condition where plasma phosphate concentration is elevated.
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PMID:Effects of parathyroid hormone and N6,O2'-dibutyryl cyclic AMP on Ca2+ transport across the rabbit distal nephron segments perfused in vitro. 626 87

Arginine vasopressin (AVP) has been shown to stimulate active Cl transport across the medullary thick ascending limb of Henle's loop (MAL) in association with an increase in adenylate cyclase activity. To determine whether the failure to demonstrate active Cl transport across the thin ascending limb of Henle's loop (TAL) in previous in vitro perfusion studies was due to the absence of AVP in the preparation, we examined the effect of AVP on adenylate cyclase activity and Cl transport in the hamsters TAL. AVP (1 mU/ml) increased adenylate cyclase activity in the hamster TAL (20.7 +/- 5.2 control vs. 46.2 +/- 10.1 fmol . mm-1 . 30 min-1, n = 6, P less than 0.05) but not in the descending limb (27.8 +/- 7.0 control vs. 20.4 +/- 2.7, n = 4, P less than 0.05). When both MAL and TAL were perfused, a lumen-positive transepithelial voltage (Vt) was observed. The Vt was increased by adding 1 or 10 mU/ml AVP to the bath. When only the TAL was perfused, the Vt was not different from zero. Similar results were obtained in mouse renal tubules. In other experiments, AVP did not affect the diffusion potential generated when a transepithelial NaCl gradient was present. AVP or dibutyryl cAMP caused little or no change in efflux of radioactive chloride across the hamster TAL. These findings suggest that electrogenic chloride transport is not demonstrable in the TAL even in the presence of AVP. The physiologic role of AVP-sensitive adenylate cyclase in the TAL remains to be established.
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PMID:Effects of arginine vasopressin on the thin ascending limb of Henle's loop of hamsters. 628 50

These studies tested the effects of isoproterenol on potassium secretion in the isolated perfused cortical collecting tubule. Isoproterenol, 10(-6) M (n = 6) and 10(-4) M (n = 2), added to bathing solution produced a significant fall in potassium secretion [13.5 +/- 1.2 to 8.0 +/- 0.9 peq X mm-1 X min-1 (P less than 0.01)] and in transepithelial voltage (P less than 0.01) compared with time controls (n = 9). Pretreatment with propranolol abolished this effect (n = 4). Addition of propranolol alone to the bath caused no significant change in potassium secretion (n = 8). 8-[p-Chlorophenylthio]cAMP (10(-4) M, isotonic perfusate) added to the bath produced a significant fall in potassium secretion [11.5 +/- 1.7 to 7.2 +/- 1.3 peq X mm-1 X min-1, n = 7 (P less than 0.01)]. Arginine vasopressin (25 microU/ml), which also stimulates adenylate cyclase activity in this segment, had no significant effect on potassium secretion (n = 10). When chloride was replaced by methyl sulfate in all solutions (n = 6), there was a significant attenuation in the fall in potassium secretion in experiments with 10(-6) M isoproterenol compared with experiments with chloride-containing bath solutions (P less than 0.05). These data suggest that isoproterenol has a specific action of reducing potassium secretion in the cortical collecting tubule either through alternating chloride transport per se or through some other effect dependent on the presence of chloride (e.g., hydrogen ion secretion). Also, this effect is probably mediated by cAMP-dependent events. The lack of effect of vasopressin on potassium secretion suggests that separate cells or cellular pools of cAMP are involved in hormonal stimulation by isoproterenol and vasopressin in this nephron segment.
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PMID:Effects of isoproterenol on potassium secretion by the cortical collecting tubule. 633 Nov 72

We examined the effects of epinephrine in perfused cortical collecting ducts (CCD) isolated from inbred Dahl-Rapp salt-sensitive (SS) and salt-resistant (SR) rats and from Sprague-Dawley (SD) rats. Rats were treated with 2.5 mg deoxycorticosterone pivalate (DOC; depot injection 4-9 days before study), and the CCD were treated with 220 pM vasopressin (AVP) to maximize Na+ transport. In CCD from all three strains 10 microM epinephrine in the bathing solution completely inhibited net Na+ transport, osmotic water permeability (Pf), and transepithelial voltage. In the SS CCD, epinephrine increased the fractional resistance of the luminal membrane to the same extent as 10 microM amiloride, indicating that it blocked the amiloride-sensitive conductance of the luminal membrane. Even at 100 nM epinephrine inhibited 80-100% of Na+ and water transport, and 1 microM yohimbine reversed or prevented these effects. In SS CCD, 0.1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) plus 0.1 mM 3-isobutyl-1-methylxanthine in place of AVP increased lumen-to-bath Na+ flux (J1-->b) from 56 +/- 5 to 143 +/- 3 pmol.min-1 x mm-1 and Pf from 6 +/- 12 to 1067 +/- 152 microns/s, but 100 mM epinephrine still significantly inhibited cAMP-stimulated J1-->b and Pf by 40 +/- 5% and 31 +/- 9%, respectively. Similar results were observed in the SR and SD rat CCD; however, the ability of yohimbine to reverse the epinephrine effect on cAMP-dependent transport was variable among the rat strains. We conclude that epinephrine acts via an alpha 2-receptor to inhibit adenylate cyclase but that at least one additional intracellular second messenger system may be involved.
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PMID:Inhibition by epinephrine of AVP- and cAMP-stimulated Na+ and water transport in Dahl rat CCD. 810 98

Ductal elements within salivary glands are responsible for modifying the electrolyte composition of primary saliva secreted by the acini. To study the mechanism and regulation of the transport processes involved requires a suitable preparation of functional ducts. To this end we have isolated intralobular ducts from rabbit mandibular salivary glands using the technique of tissue dissociation and microdissection. Light and electron microscopy demonstrated that the ducts corresponded ultrastructurally to striated intralobular ducts of the intact gland. Ducts could be maintained in tissue culture on polycarbonate filter rafts for up to 36 h, during which time the ends of the ducts did not usually seal. The overall resting content of ductal adenosine 3',5'-cyclic monophosphate (cyclic AMP) was 16.0 +/- 3.0 fmol mm-1 and increased dose dependently in response to stimulation with the beta-adrenoceptor agonist isoprenaline (10(-9)-10(-4) M; concentration required to produce a half-maximal response, K0.5 = 2.1 x 10(-6) M). The response to isoprenaline was blocked by the antagonist propranolol. Intracellular cyclic AMP content was also raised by the adenylate cyclase activator forskolin and by prostaglandin E2. Acetylcholine (3 x 10(-8)-10(-5) M) caused a dose-dependent and maintained rise in [Ca2+]i (K0.5 = 2.5 x 10(-7) M). This increase in [Ca2+]i could be reversed by the muscarinic antagonist atropine and appeared to result from a combination of mobilization of intracellular Ca2+ stores and entry of Ca2+ from the extracellular fluid. Noradrenaline induced only a very small, mainly transient rise in [Ca2+]i while phenylephrine failed to increase [Ca2+]i at all. Vasoactive intestinal peptide (5 x 10(-7) M) also produced a marginal, maintained rise in [Ca2+]i. Substance P, bombesin, isoprenaline, and prostaglandin E2 did not elevate [Ca2+]i. Application of the calcium ionophore ionomycin induced a substantial maintained rise in [Ca2+]i. Taken together, these results indicate that isolated and cultured striated ducts (i) possess intact beta-adrenoceptors coupled to adenylate cyclase, putative receptors for prostaglandin E2 and muscarinic receptors, and (ii) represent a viable preparation for the study of the transport mechanisms involved in the ductal modification of salivary fluid composition.
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PMID:Structural and functional characterization of striated ducts isolated from the rabbit mandibular salivary gland. 838 3


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