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)

The beta-adrenoceptor in the intermediate lobe (IL) of the hypophysis of the rat is characterized on the basis of the following: 1) the ability of beta-adrenergic agonists to increase adenylate cyclase activity in homogenates of the IL, and 2) the ability of drugs active upon the beta-adrenoceptor to compete with [125I]hydroxybenzylpindolol, a radiolabeled beta-adrenergic antagonist, for high affinity (Kd = 232 pM) binding sites. The values of the affinity of the beta-adrenoceptor for drugs obtained in either assay system are in good agreement. The relative potency among agonists, L-isoproterenol greater than L-epinephrine greater than L-norepinephrine, suggests that the receptor is of the beta-2 subcategory. cAMP, derivatives of cAMP, and a phosphodiesterase inhibitor, theophylline, mimic the ability of l-isoproterenol to enhance the release of alpha MSH from dispersed cells of the rat IL. The present results are in accord with the possibility that occupancy by agonists of the beta-adrenoceptor of the IL enhances adenylate cyclase activity, resulting in an accumulation of cAMP which initiates the intracellular events that are ultimately expressed as an enhanced release of alpha MSH. Pharmacological data suggest that stimulation of a dopamine receptor in the IL diminishes the response of the beta-adrenoceptor to agonists.
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PMID:Biochemical identification of the beta-adrenoceptor and evidence for the involvement of an adenosine 3',5'-monophosphate system in the beta-adrenergically induced release of alph-melanocyte-stimulating hormone in the intermediate lobe of the rat pituitary gland. 610 99

The dopamine receptor in the intermediate lobe (IL) of the hypophysis of the rat is characterized on the basis of the ability of dopamine and other dopaminergic agonists to decrease the consequences of activation of the beta-adrenoceptor. Stimulation of the dopamine receptor diminishes the L-isoproterenol-induced accumulation of cAMP and the catecholamine-stimulated enhancement of adenylate cyclase activity. The dopamine receptor in the IL can be assigned to the category of dopamine receptor designated D-2 on the basis of the following criteria: 1) occupancy of the dopamine receptor does not result in enhancement of adenylate cyclase activity or an accumulation of cAMP, 2) the dopaminergic ergots and apomorphine mimic the inhibitory effect of dopamine upon cAMP formation or alpha MSH release, and 3) metoclopramide and sulpiride, substituted benzamides, block the inhibitory effect of dopamine. The sympathetic neurotransmitter, norepinephrine, interacts with the dopamine receptor and the beta-adrenoceptor in the IL.
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PMID:The dopamine receptor in the intermediate lobe of the rat pituitary gland: pharmacological characterization. 610 42

Partially purified plasma membrane preparations from the inner zones of the rat adrenal exhibit a specific and high affinity for a pro-gamma MSH peptide, synthetic rat Lys-[125I-iodo-Tyr1] gamma 3MSH, that is time and temperature dependent, reversible, and saturable. Studies with demedullated adrenals indicate that at least part of this binding is to the adrenal cortex. Scatchard analysis reveals a single class of binding sites (101 fmol/mg membrane protein) for the radioactive ligand, with an apparent Kd of 0.74 nM. However, this may understate the receptor affinity for native pro-gamma MSH(s), because the binding capacity of Lys-gamma 3MSH is impaired somewhat by iodination. Lys-[125I-iodo-Tyr1] gamma 3MSH exhibits a 100-fold higher affinity for the binding site than ACTH-(1-24), but unlike ACTH, concentrations of Lys-gamma 3MSH up to 10 microM fail to stimulate membrane-associated adenylate cyclase activity. Guanylate cyclase in this subcellular fraction also is unresponsive to Lys-gamma 3MSH. Results obtained with crude membrane fractions from other rat tissues suggest that specific pro-gamma MSH binding may not be unique to the adrenal cortex.
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PMID:Lys-gamma 3-melanotropin binds with high affinity to the rat adrenal cortex. 613 11

Stimulation of the release of alpha MSH from dispersed rat melanotrophs by L-isoproterenol, 8-bromo-cAMP, or cholera toxin requires calcium ion (Ca++) in the incubation medium; the stimulatory effect of each of these agents is attenuated by D-600, a Ca++ antagonist. In contrast, stimulation of the formation of cAMP by L-isoproterenol, isobutyl methylxanthine, or cholera toxin does not require Ca++ in the incubation medium. Ca++ diminishes the amount of cAMP formed by cholera toxin-treated melanotrophs. Ca++ inhibits adenylate cyclase activity and enhances cyclic nucleotide phosphodiesterase activity in cell-free homogenates of intermediate lobe tissue. A23187, a calcium ionophore, increases the accumulation of 45Ca by melanotrophs and enhances the release of alpha MSH. Furthermore, when tested upon cholera toxin-treated melanotrophs, A23187 potentiates the Ca++-induced inhibition of cAMP formation. The results indicate that Ca++ is essential for the release of alpha MSH, and that cAMP in some way enhances the effects of Ca++ upon the release process.
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PMID:Coordinated action of calcium ion and adenosine 3',5'-monophosphate upon the release of alpha-melanocyte-stimulating hormone from the intermediate lobe of the rat pituitary gland. 617 17

The number of ACTH-(1-24) receptors and the adenylate cyclase (AC) responsiveness to several stimuli have been measured in crude adrenal membranes from fetal and newborn lambs. At 124 days of gestation, the number of ACTH-(1-24)-binding sites was 51 +/- 9 (SE) pmol/microgram DNA, and AC was stimulated by 2 x 10(-2) M NaF (195 +/- 5%) and 10(-5) M guanosine (beta, gamma-imido) triphosphate [Gpp(NH)p]; (168 +/- 8%) but not by 10(-6) M ACTH-(1-24). However, when Gpp(NH)p was added to ACTH-(1-24), the response was significantly higher than with Gpp(NH)p alone. On the contrary, at 140 days, despite no increase in the number of ACTH-(1-24) receptors, AC was stimulated by ACTH-(1-24) (135 +/- 6%), and Gpp(NH)p enhanced this response. In addition, the response to NaF and to Gpp(NH)p alone was higher at 140 than at 124 days. Between day 140 of gestation and birth, the stimulation of AC by ACTH-(1-24) and ACTH-(1-24) plus Gpp(NH)p increased, but the response to NaF and to Gpp(NH)p alone did not. During the same time, the number of ACTH-(1-24) receptors was increased by a factor of 3. No change in the Kd and Km of ACTH-(1-24) was observed during the period studied. Neither prostaglandin E2 (10(-5) M) nor alpha MSH (10(-6) M) stimulated AC at any stage. The relative insensitivity of AC before 140 days can thus be related to 1) a defect of availability of GTP, and 2) a low activity of the catalytic subunit of AC (subunit C) or, alternatively, a defect in the GTP-binding component (subunit N). The increased sensitivity to ACTH-(1-24) of the enzyme just before parturition correlates closely with an increase in the number of ACTH-(1-24) receptors.
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PMID:Maturation of adrenocorticotropin-sensitive adenylate cyclase of ovine fetal adrenal during late pregnancy. 626 49

Melanocyte-stimulating hormone (alpha-melanotropin, MSH) may function in a number of diverse physiological roles. MSH stimulates (1) rapid translocation of melanosomes (melanin granules) in dermal melanophores to effect rapid colour change and (2) melanogenesis in normal and abnormal (melanoma) epidermal melanocytes. Both actions involve (1) initial binding of the peptide on the melanocyte membrane, (2) transduction of signal to adenylate cyclase, and (3) increased cytosolic levels of cyclic AMP. Efforts to prepare radioiodinated MSH and analogues for radioreceptor studies using melanoma membranes and intact cells reveal that conventional iodination procedures inactivate the hormone because of oxidative and iodination effects on specific structural components of the peptide. These effects can be circumvented by the use of synthetically tailored MSH analogues. Transduction of signal from receptor to adenylate cyclase requires calcium, but prostaglandin or beta-adrenoceptor stimulation of melanophores does not. The nucleotide and metal ion requirements for mouse melanoma adenylate cyclase activity have been characterized. There is both a transcriptional and translational requirement for MSH stimulation of tyrosinase activity and melanin production in melanoma cells. Melanosome translocation within melanophores is enhanced in the absence of extracellular calcium. A model for the MSH control of melanosome movements suggests a bifunctional, but compartmentalized, role for calcium in the action of MSH.
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PMID:Biological actions of melanocyte-stimulating hormone. 626 80

1 The primary effect of catecholamines was to lighten Anolis skin previously darkened by alpha-melanocyte-stimulating hormone (alpha-MSH). In concentrations above 10(-7) M noradrenaline, 10(-6) M adrenaline and 10(-5) dopamine, darkening of subpopulations of melanophores occurred. Subsequent experiments were concerned with the effect of low catecholamine concentrations on alpha-MSH action. 2 The relationship between MSH receptors and alpha-adrenoceptors on the Anolis melanophore was studied by a kinetic approach using the rate bioassay method and by use of alpha-adrenoceptor agonists and antagonists. 3 alpha-MSH dose-response curves were shifted, in parallel, to the right in the presence of the catecholamines, noradrenaline, adrenaline and dopamine, and Lineweaver-Burke plots and Arunlakshana-Schild plots indicated that the catecholamines antagonized MSH action by a competitive mechanism. 4 Phentolamine had an inhibitory effect on the action of adrenaline but not on the action of MSH. Therefore MSH and catecholamine actions were mediated by separate receptors. 5 The classical kinetics of competition are not confined to competition at a single receptor. 6 The alpha-adrenoceptor was defined as the alpha 2-subtype since (a) the alpha 2-selective agonist, clonidine, was found to mimic catecholamine action. (b) The alpha 2-selective antagonist, yohimbine, blocked the actions of clonidine and adrenaline. (c) The alpha 1-selective antagonist, prazosin, had negligible blocking effects on adrenaline and clonidine. 7 We conclude that a close association exists between the separate MSH receptor and alpha 2-adrenoceptor on the Anolis melanophore. The competition that takes place between MSH and catecholamines must occur after hormone-receptor interaction, possibly through a common adenylate cyclase moiety oppositely controlled by the two receptors involved.
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PMID:The association between the melanocyte-stimulating hormone receptor and the alpha 2-adrenoceptor on the Anolis melanophore. 628 Jul 99

No reliable answer can yet be given whether the pituitary gland is physiologically involved in the process of fat mobilization. The reasons are, for example, different test systems and criteria of lipolytic activity as well as variable criteria of purity of the peptides tested. Under comparable test conditions MSH, beta-endorphin, ACTH and beta-lipotropin turned out to be the most lipolytically active peptides. There is also increasing evidence that these peptides are involved in metabolic processes especially in glucose metabolism. The lipolytic activity of beta-lipoprotein, ACTH and MSH is mediated by a common heptapeptide (beta-LPH 47-53) furthermore, beta-lipotropin has a second message sequence in the C-terminal part of its molecule (beta-endorphin). This second message sequence is located in the amino acid sequence beta-LPH 77-86. The lipolytic effect of all these peptides is accompanied by an activation of adenylate cyclase. The effect of beta-endorphin is not mediated by an opiate receptor. The further elucidation of the lipolytic activity of these peptides investigations were necessary on the degradation of the peptides at the site of action as well as the use of test systems nearer to physiological conditions for example perifused fat cells. In conclusion, there are condensing data on the possible physiological role of brain and pituitary peptides in metabolic regulation.
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PMID:Effects of pituitary peptides on fat mobilisation. 628 82

Forskolin stimulates adenylate cyclase activity in a cell-free homogenate of the intermediate lobe (IL) of the rat pituitary gland. L-Isoproterenol, a beta-adrenergic agonist, enhances and apomorphine, a D-2 agonist, inhibits the forskolin-stimulated adenylate cyclase activity. Guanosine triphosphate is obligatory for the dopaminergic attenuation of the forskolin-enhanced enzyme activity. When tested upon enzymatically dispersed IL cells, forskolin enhances the release of both cAMP and immunoreactive alpha MSH-like peptides. These effects of forskolin upon the IL are discussed within the context of a previously published working hypothesis that cAMP in some way triggers the calcium-dependent release of hormones from the IL.
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PMID:Forskolin stimulates adenylate cyclase activity, adenosine 3',5'-monophosphate production and peptide release from the intermediate lobe of the rat pituitary gland. 632 Nov 38

After treatment with cholera toxin, homogenates of intact intermediate lobe (IL) tissue of rat pituitary gland synthesized more cAMP than did homogenates of untreated IL tissue, and only in the presence of GTP did dopamine or apomorphine diminish the elevated adenylate cyclase activity in homogenates of cholera toxin-treated IL tissue. Furthermore, when tested on cholera toxin-treated IL tissue, 5'-guanylyl imidodiphosphate [Gpp(NH)p] and two other nonhydrolyzable analogs of GTP inhibited adenylate cyclase activity in the absence of either a dopaminergic agonist or GTP; GTP reversed the Gpp(NH)p-induced inhibition of adenylate cyclase activity. Apomorphine, a dopaminergic agonist, abolished the ability of GTP to reverse the inhibition by Gpp(NH)p; this effect of apomorphine was prevented by fluphenazine, a dopaminergic antagonist. Sodium fluoride inhibited adenylate cyclase activity to approximately the same level obtained with GTP and apomorphine. In addition, apomorphine decreased cAMP accumulation and alpha MSH release from dispersed IL cells pretreated with cholera toxin.
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PMID:D-2 dopamine receptor-mediated inhibition of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland requires guanosine 5'-triphosphate. 705 33


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