D-2 Dopamine Receptor-Mediated Inhibition of Adenylate Cyclase Activity in the Intermediate Lobe of the Rat Pituitary Gland Requires Guanosine 5'-Triphosphate

The intermediate lobe (IL) of the rat pituitary gland responds to catecholamines. Catecholamines interacting with the β-adrenoceptor stimulate adenylate cyclase activity, enhance cyclic AMP formation and thereby trigger the release of α-melanocyte-stimulating hormone (α-MSH). Catecholamines interacting with a D-2 dopamine receptor (in the classification schema of Kebabian and Calne) diminish adenylate cyclase activity and thereby decrease the capacity of IL cells to synthesize cyclic AMP. Dopaminergic agonists also inhibit the release of α-MSH from IL cells. The homogeneity of the IL facilitates biochemical investigations of this tissue.

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“…2A). Second, cholera toxin increases the formation of cAMP by intact rat IL cells [7,33,34] (fig. 3A).…”

Section: (I-adrenoceptormentioning

confidence: 99%

Biochemical and Physiological Studies of the Beta-Adrenoceptor and the D-2 Dopamine Receptor in the Intermediate Lobe of the Rat Pituitary Gland: A Review

Côté¹,

Eskay²,

Frey³

et al. 1982

Neuroendocrinology

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136

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“…In a number of systems it is well established that activation of D 2 receptor results in multiple signaling mechanisms including inhibition of adenylate cyclase [46][47], inhibition of phosphoinositide turnover [48][49][50], and activation of potassium channels [51]. We further investigated the potential signaling mechanisms involved in the dopamine mediated inhibition of NPY-ir release.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of dopamine mediated inhibition of neuropeptide Y release from pheochromocytoma cells (PC12 cells)

Gui-Hua¹,

Gardner²,

Westfall³

2007

Biochemical Pharmacology

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In rat pheochromocytoma (PC-12) cells the dopamine D 2 receptor agonists apomorphine (APO) and n-propylnorapomorphine (NPA) produced a concentration dependent inhibition of K + -evoked neuropeptide Y release (NPY-ir). The effect of APO was blocked by the dopamine D 2 -receptor antagonist, eticlopride, but not the D 1 /D 3 or the D 4 /D 2 antagonists, SCH23390 or clozapine, respectively. The D 1 /D 5 receptor agonist, SKF38393 or the D 3 agonists PD128907 and 7-OH DPAT had no effect. Selective N and L-type voltage gated Ca 2+ channel blockers, ω-Conotoxin GVIa (CtxGVIa) and nifedipine, respectively, produced a concentration dependent inhibition of NPY-ir release but were not additive with APO. The Ca 2+ /calmodulin-dependent protein kinase (CaM kinase) II inhibitor KN-62 produced a concentration-dependent inhibition of NPY-ir release but the combination of KN-62 and APO produced no further inhibition. PMA-mediated protein kinase C stimulation significantly increased both basal and K + -evoked release of NPY-ir, and in the presence of PMA APO had no inhibitory effect. The PKC antagonist, chelerythrine, inhibited K + -evoked NPYir release but was not additive with APO. Neither forskolin-mediated adenylate cyclase activation and the active cAMP analog Sp-cAMPS, nor the adenylate cyclase inhibitor SQ 22536, and the competitive inhibitor of cAMP-dependent protein kinases Rp-cAMPS, had any significant effect on K + -evoked NPY-ir release. This suggests the inhibitory effect of APO on K + -evoked release of NPYir from PC 12 cells is most likely mediated through activation of dopamine D 2 receptors leading to direct inhibition of N and L-type voltage gated Ca 2+ channels, or indirect inhibition of PKC, both of which would reduce [Ca 2+ ] i and inactivate CaM kinase.

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“…For example, treatment of membrane preparations or intact cells with N-ethylmaleimide or trypsin can obliterate hormone and guanine nucleotideinduced adenylate cyclase inhibition, whereas hormone and guanine nucleotide-induced adenylate cyclase stimulation is unaffected or even increased (4)(5)(6)(7)(8). Furthermore, cholera toxin, which activates the adenylate cyclase through a covalent modification of the stimulatory guanine nucleotide site (9, 10), does not affect hormone-induced adenylate cyclase inhibition (11)(12)(13)(14)(15)(16).…”

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confidence: 99%

“…The assays were performed in triplicates with an intraassay variation (SD) of <5% of the means and were repeated at least three times with identical results to those shown herein. RESULTS Forskolin (30 ,uM) elevated cyclic AMP levels in S49 lymphoma cyc variants 10-fold when added for 15 methylxanthine (30 MM). Most of the cyclic AMP (measured under stimulated conditions) was contained by the cells; only 21% was found in the medium.…”

mentioning

confidence: 99%

“…Therefore, cholera toxin does not affect the hormone-induced adenylate cyclase inhibition (11)(12)(13)(14)(15)(16) and also does not increase the cyc-adenylate cyclase inhibition by GTP (21), whereas the toxin increases adenylate cyclase stimulation by GTP in other cell types (9,10 and Ni, which are under the influence of stimulatory and inhibitory hormones, respectively, acting through their specific receptors.…”

mentioning

confidence: 99%

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Occurrence of a hormone-sensitive inhibitory coupling component of the adenylate cyclase in S49 lymphoma cyc- variants.

Jakobs¹,

Schultz²

1983

Proc. Natl. Acad. Sci. U.S.A.

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The influence of somatostatin was studied on cyclic AMP levels and adenylate cyclase activity in cyc-variants of S49 lymphoma cells. These cells are deficient in the guanine nucleotide site that mediates hormone-induced adenylate cyclase stimulation, but their cyclase can be stimulated by forskolin. Somatostatin maximally decreased the 30 ,LM forskolin-stimulated cyclic AMP levels by 35%. Half-maximal suppression occurred at about 0.1 nM somatostatin. Somatostatin (up to 1 ,LM) had no effect on the 100 ,LM forskolin-stimulated adenylate cyclase activity in cycmembrane preparations when guanine nucleotides were not present. In the presence of GTP, however, which by itself caused a small decrease in activity, somatostatin maximally inhibited the enzyme by 20-25%. GTP was half-maximally effective at O.1 j.M, and half-maximal inhibition by somatostatin was observed at 0.1-1 nM. In the presence of the stable GTP analog guanosine 5'-O-(3-thiotriphosphate) (1 ,uM), which decreased the stimulated activity by about 40% after a short lag period, somatostatin (1 ,uM) did not cause a further decrease in final activity but reduced the lag period by about 50%. The data indicate that membranes of cyc variants contain a regulatory site that mediates both guanine nucleotide and hormone-induced inhibition of the adenylate cyclase and suggest that the mechanisms of activation and inactivation of this inhibitory site are similar to those of the stimulatory component missing in cyc-membranes.

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D-2 Dopamine Receptor-Mediated Inhibition of Adenylate Cyclase Activity in the Intermediate Lobe of the Rat Pituitary Gland Requires Guanosine 5'-Triphosphate

Cited by 85 publications

References 12 publications

Biochemical and Physiological Studies of the Beta-Adrenoceptor and the D-2 Dopamine Receptor in the Intermediate Lobe of the Rat Pituitary Gland: A Review

Biochemical and Physiological Studies of the Beta-Adrenoceptor and the D-2 Dopamine Receptor in the Intermediate Lobe of the Rat Pituitary Gland: A Review

Mechanism of dopamine mediated inhibition of neuropeptide Y release from pheochromocytoma cells (PC12 cells)

Occurrence of a hormone-sensitive inhibitory coupling component of the adenylate cyclase in S49 lymphoma cyc- variants.

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