To investigate whether a particular receptor subtype can be coupled to multiple effector systems, recombinant M2 muscarinic receptors were expressed in cells lacking endogenous receptor. The muscarinic agonist carbachol both inhibited adenylyl cyclase and stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was significantly less efficient and more dependent on...

Mammalian adenylyl cyclases have two homologous cytoplasmic domains (C1 and C2), and both domains are required for the high enzymatic activity. Mutational and genetic analyses of type I and soluble adenylyl cyclases suggest that the C2 domain is catalytically active and the C1 domain is not; the role of the C1 domain is to promote the catalytic activity of the C2 domain. Two amino acid residues...

With use of a discontinuous sucrose density gradient centrifugation in the presence of 1 mM EDTA and 10 mM Trls-HCl, pH 7.5, membrane particles were prepared from beef renal medulla that are 4to B-fold enriched in fluoridesensitive and 8to 12-fold enriched in neurohypophyseal hormone (NHH)-sensitive adenylyl cyclase activity. Average yield of the NHH-sensitive adenylyl cyclase activity was 30 t...

The second messenger cAMP is involved in a number of cellular signaling pathways. In mammals, cAMP is produced by either the hormonally responsive, G protein-regulated transmembrane adenylyl cyclases (tmACs) or by the bicarbonate- and calcium-regulated soluble adenylyl cyclase (sAC). To develop tools to differentiate tmAC and sAC signaling, we determined the specificity and potency of commercia...

Odor transduction mediated by the adenylyl cyclase/cAMP pathway has been well studied, but it is still uncertain whether this pathway mediates the transduction of all odors in vertebrates. We isolated olfactory sensory neurons from the salamander Necturus maculosus and used calcium imaging with the indicator dye fura-2 to examine olfactory responses elicited by amino acids. The properties of ap...

Huntington’s disease (HD) is a neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding for Huntingtin (Htt), which results in progressive degeneration of the striatal GABAergic/enkephalin neurons. These neurons express both the A2A and D2 receptors, which stimulate and inhibit adenylyl cyclase, respectively. In this study we analyzed the possibility of an involvement...

It is well established that G protein-coupled receptors stimulate nitric oxide-sensitive soluble guanylyl cyclase by increasing intracellular Ca(2+) and activating Ca(2+)-dependent nitric-oxide synthases. In pituitary cells receptors that stimulated adenylyl cyclase, growth hormone-releasing hormone, corticotropin-releasing factor, and thyrotropin-releasing hormone also stimulated calcium signa...

Mammals have nine differentially regulated isoforms of G protein-responsive transmembrane-spanning adenylyl cyclases. We now describe the existence of a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or Forskolin regulation. Northern analysis indicates the gene encoding soluble adenylyl cyclase (sAC) is preferentially expressed in testis. As purified f...

The effects of chronic treatment with desimipramine (a tricyclic antidepressant), fluoxetine [a specific 5-hydroxytryptamine (5-HT) uptake inhibitor], clorgyline (a specific monoamine oxydase inhibitor of A type), ipsapirone (a specific 5-HT1A receptor agonist) as well as electroconvulsive shock treatment were investigated on rat hippocampal 5-HT1A receptors negatively coupled to adenylyl cycla...

The present study investigated whether high salt intake (8%) in Dahl salt-sensitive and salt-resistant rats with and without hypertension produces a heterologous desensitization of cardiac adenylyl cyclase as observed in various types of hypertension and human heart failure. In membranes from Dahl salt-sensitive rats on a high-salt diet (8%) basal, isoproterenol-, 5'-guanylylimidodiphosphate-, ...