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)

alpha-Bag cell peptide (alpha-BCP), one of the secretory products of the neuroendocrine bag cells in Aplysia, has been reported by various investigators to have either excitatory or inhibitory feedback effects. Though conflicting, these results may be explained by the difference in temperature at which the experiments were performed. Because egg laying in this animal is temperature dependent, the alteration in function of this peptide by temperature may offer a possible molecular basis for the seasonal regulation of egg laying. This hypothesis was investigated by assessing the feedback actions of alpha-BCP at various temperatures. At 15 degrees C, alpha-BCP hyperpolarized bag cells, shortened the duration of synaptically evoked bag cell discharges, and reduced the number of action potentials per discharge. However, at 20 degrees C, the peptide depolarized bag cells, lengthened discharges, and increased the number of action potentials per discharge. A temperature-dependent influence on bag cell cAMP levels may underlie these effects, because alpha-BCP reduced basal cAMP levels in intact bag cells at temperatures of 15 degrees C and below, while at 17-22 degrees C it increased these levels. However, the inhibitory effects of alpha-BCP on stimulated adenylate cyclase activity in bag cell homogenates were not temperature dependent. Moreover, a low-Ca2+/high-Mg2+ solution abolished alpha-BCP's ability to increase bag cell cAMP levels at 20 degrees C. This suggests that the peptide may evoke the secretion of an excitatory modulator at the higher temperature. These results imply that alpha-BCP is autoinhibitory at typical winter temperatures, but becomes autoexcitatory as ocean temperature rises in the summer. Thus, the peptide may function in coordination with other factors to regulate egg laying in response to seasonal temperature variations.
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PMID:Temperature-dependent peptidergic feedback: potential role in seasonal egg laying in Aplysia. 171 Jun 58

alpha-Bag cell peptide (alpha-BCP), one of several secreted peptides encoded in the precursor to the egg-laying hormone (proELH) of the neurosecretory bag cells of Aplysia, has been variously reported to have autoexcitatory or autoinhibitory effects on the cells which secrete it. Since we had found previously that alpha-BCP reduces stimulated cAMP levels in intact bag cells, an effect that would be consistent with electrophysiological inhibition, we investigated the direct effect of the peptide on adenylate cyclase in bag cell membrane preparations. alpha-Bag cell peptide did not affect basal adenylate cyclase activity, but reduced forskolin-stimulated activity by about 30%. The potency of the peptide in this assay was within the range reported for observable physiological effects: half-maximal inhibition was seen at approximately 100 nM peptide. Both basal and forskolin-stimulated enzyme activity were dependent on GTP, and the inhibitory effect of alpha-BCP was inversely dependent on the nucleotide. The non-hydrolyzable analogue, GTP-gamma-S, stimulated both basal and forskolin-stimulated enzyme activity and enhanced alpha-BCP's effect to the extent that the peptide completely inhibited forskolin's stimulation of the enzyme. The peptide's effect could be blocked by pretreatment with pertussis toxin. We conclude that alpha-BCP inhibits bag cell adenylate cyclase, an effect which is consistent with an autoinhibitory role in bag cell function. Moreover, this inhibition appears to be mediated by a GTP-binding protein.
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PMID:Alpha-bag cell peptide inhibits bag cell adenylate cyclase via a GTP-dependent mechanism. 216 71

Brief electrical or hormonal stimulation of the bag cell neurons of Aplysia triggers a long-lasting discharge during which alpha bag cell peptide (alpha-BCP) and other neuropeptides are released from the cells. We have carried out experiments, using both intact abdominal ganglia and isolated neurons, demonstrating that alpha-BCP acts directly on the bag cell neurons to influence cAMP levels and voltage-dependent potassium currents. Exposure of the bag cell neurons within intact ganglia to alpha-BCP, at concentrations greater than 1 nM, inhibited an ongoing discharge. alpha-BCP also significantly reduced both basal and forskolin-stimulated levels of cAMP in bag cell clusters. The inhibition of the discharge by alpha-BCP could be prevented and reversed by pharmacological elevation of intracellular cAMP levels. Immunohistochemical staining of neurons maintained in cell culture showed that all isolated bag cell neurons exhibit immunoreactivity with antisera against alpha-BCP. Application of the adenylate cyclase activator forskolin to such isolated cells, in the presence of a phosphodiesterase inhibitor, attenuates the amplitude of the delayed voltage-dependent outward currents measured in voltage-clamp experiments. Pretreatment of the cells with alpha-BCP significantly reduced the ability of forskolin to attenuate these currents, demonstrating that alpha-BCP acts directly at autoreceptors on bag cell neurons. Experiments with the isolated cells showed that a second autoreceptor-mediated effect of alpha-BCP was the enhancement of an inwardly rectifying potassium current that was activated at potentials more negative than -40 mV. The reversal potential and conductance of the current induced by alpha-BCP were dependent on the external K+ concentration. This response to alpha-BCP could be blocked by rubidium, cesium, and barium ions. Our data demonstrate that alpha-BCP can exert inhibitory biochemical and electrophysiological actions on the bag cell neurons that release it and suggest that autoreceptors for alpha-BCP play an important role in the termination of a discharge in the bag cell neurons.
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PMID:Alpha bag cell peptide directly modulates the excitability of the neurons that release it. 282 16

The bag cell peptides (alpha-, beta-, and gamma-BCP) are secreted by the neuroendocrine bag cells of Aplysia, and provide feedback modulation of bag cell excitability and cAMP levels. We report here that if 200-500 mM NaCl is included in the assay buffer, the BCPs alter adenylate cyclase activity in a manner consistent with their effects on cAMP levels in intact bag cells. Specifically, beta-BCP and the related peptide A from the atrial gland stimulate the enzyme, while the effects of alpha-BCP(1-7) and gamma-BCP are temperature-dependent, stimulating at 30 degrees C and inhibiting at 15 degrees C. Both stimulation and inhibition require GTP, suggesting mediation by Gs and Gi. The ionic requirements of stimulation and inhibition differ: Cl- is necessary to support stimulation, but not inhibition. Moreover, pertussis toxin blocks inhibition, but does not affect stimulation. These results suggest that the temperature-sensitive mechanism lies upstream from the G-proteins in the signal transduction pathway.
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PMID:Temperature-dependent stimulation and inhibition of adenylate cyclase by Aplysia bag cell peptides. 838 57