guanosine-triphosphate and hydroxybenzylisoproterenol

Topics: Adenosine Triphosphate; Adrenergic beta-Agonists; Albuterol; Animals; Binding, Competitive; Cell Line; Cell Membrane; Guanosine Triphosphate; Isoproterenol; Lymphoma; Mice; Pindolol; Receptors, Adrenergic, beta; Stereoisomerism; Structure-Activity Relationship

P815, a murine mastocytoma cell line, possesses beta-adrenergic binding sites as assessed by using [3H]dihydroalprenolol (antagonist) and [3H]hydroxybenzylisoproterenol (agonist). The number of binding sites per cell was 29 000 for the agonist and 75 000 for the antagonist, as determined by direct binding assays and inhibition experiments on intact cells. On membrane preparations from the same cells, binding of alprenolol was only displaceable by antagonists, while stereospecific binding of hydroxybenzylisoproterenol was only displaceable by agonists. The P815 membranes also possessed an adenylate cyclase stimulated by Gpp(NH)p and NaF but not by 1-isoproterenol. The intracellular cAMP level of intact cells was not modulated by 1-isoproterenol or by 1-epinephrine, but was increased by forskolin. These results suggest that the beta-adrenergic receptor of P815 mastocytoma cells is non-functional. This may explain the failure of agonists to stimulate adenylate cyclase activity in these cells.

Topics: Adenylyl Cyclases; Animals; Cell Line; Cell Membrane; Colforsin; Cyclic AMP; Dihydroalprenolol; Diterpenes; Guanosine Triphosphate; Guanylyl Imidodiphosphate; Isoproterenol; Mast-Cell Sarcoma; Mice; Mice, Inbred DBA; Neoplasm Proteins; Receptors, Adrenergic, beta; Sarcoma, Experimental; Sodium Fluoride

Neurotransmitters and hormones mediate their effects through interaction with specific receptors. A complete understanding of the effects of these chemical signals requires detailed knowledge, at the molecular level, of agonist/receptor interactions. It is likely that agonists and antagonists interact with the same site on a receptor. Agonists, however, are by definition different from antagonists in that agonists are responsible for transducing information across the cell membrane, ultimately resulting in a biological response, while antagonists appear to act through passive occupancy of receptors. Implicit in this concept is the idea that these fundamental differences between agonists and antagonists arise from the sequelae induced by agonist-specific interactions with receptors.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Epinephrine; Guanosine Triphosphate; Humans; Isoproterenol; Magnesium; Models, Biological; Pindolol; Radioligand Assay; Receptors, Adrenergic, beta; Sulfhydryl Reagents; Thermodynamics