Accumulations of Cyclic AMP in Adenine‐Labeled Cell‐free Preparations from Guinea Pig Cerebral Cortex: Role of α‐Adrenergic and H₁‐Histaminergic Receptors

Abstract

Norepinephrine, histamine, adenosine, glutamate, and depolarizing agents elicit accumulations of radioactive cyclic AMP from adenine-labeled nucleotides in particulate fractions from Krebs-Ringer homogenates of guinea pig cerebral cortex. The particulate fractions contain sac-like entities, which apparently are associated with a significant portion of the membranal adenylate cyclase. Particulate fractions from sucrose homogenates are a less effective source of such responsive entities. Activation of the adenine-labeled cyclic AMP-generating systems by norepinephrine is by means of alpha-adrenergic receptors, while activation by histamine is through H1- and H2-histaminergic receptors. Adenosine responses are potentiated by the amines and are antagonized by alkylxanthines. Glutamate and depolarizing agents appear to elicit accumulations of cyclic AMP via "release" of endogenous adenosine. It is proposed, based on the virtual absence of an alpha-adrenergic or H1-histaminergic response in the presence of a combination of potent adenosine and H2-histaminergic antagonists, that alpha-adrenergic and H1-histaminergic receptor mechanisms do not activate adenylate cyclase directly in brain slices or Krebs-Ringer particulate fractions, but merely facilitate activation by beta-adrenergic, H2-histaminergic, or adenosine receptors.

Regulatory influence of histamine receptor activation and inhibition on the synthesis and level of hypothalamic histamine

“…These findings indicate a multiple localization of histamine'receptors and suggest that at least one part of the receptors is associated with neurons. There is also evidence that both neuronal and non-neuronal HA-receptors are coupled with specific adenylate cyclase systems [20][21][22].…”

Changes in actin dynamics and F-actin structure both in synaptoneurosomes of LRRK2(R1441G) mutant mice and in primary human fibroblasts of LRRK2(G2019S) mutation carriers

“…For electron micrographs synaptoneurosomes of LRRK2-knockout mice were prepared as described above. The samples were fixed and processed as described previously (Daly et al, 1980;Hollingsworth et al, 1985) and embedded in Epon (Fluka, Munich, Germany). Ultrathin sections were cut on an ultra microtome (Reichert, Depew, NY, USA), contrasted in lead-uranyl acetate and imaged using a Zeiss EM10 transmission electron microscope (Zeiss, Oberkochen, Germany) operating with an acceleration voltage of 120 kV and connected to a CCD camera (1024 Â 1024 pixels; TVIPS GmbH, Gauting, Germany).…”

Rapid isolation of synaptoneurosomes and postsynaptic densities from adult mouse hippocampus

“…There are some morphological criteria to identify synaptosomes, including small mitochondria within a sealed plasma membrane, synaptic vesicles present in nerve terminals, and an electron-dense membrane resembling postsynaptic membranes adhering to the periphery of the synaptosome (Whittaker, 1993). To achieve an enrichment in neuronal markers, several studies reported the use of a crude particulate fraction containing presynaptic and postsynaptic vesicularized components (Daly et al, 1980;Horn and Phillipson, 1976;Shimizu et al, 1975). The term synaptoneurosome is suggested for entities in which a presynaptic sac (synaptosome) is attached to a resealed postsynaptic sac (neurosome) Quinlan et al, 1999).…”