A serotonin sensitive guanylate cyclase associated with specific neurotransmitter binding sites on isolated synaptic membranes from mature rat brain. |
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Authors: | E S Quayle J Pagel J A Monti S T Christian |
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Affiliation: | 1. The Neurosciences Program, The University of Alabama in Birmingham Medical Center, Birmingham, Alabama 35294, USA;2. The Departments of Neurology and Psychiatry, The University of Alabama in Birmingham Medical Center, Birmingham, Alabama 35294, USA |
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Abstract: | Results from this study indicate that adult rat brain posesses guanylate cyclase activity sensitive to serotonin (5-HT) and localized in the synaptic plasma membrane. The enzyme appears to have multiple activation sites for 5-HT with specific activity maxima at the 5-HT concentrations of 5 × 10?10M and 7 × 10?8M respectively. The rates of guanosine-3′:5′-monophosphate (cyclic GMP) formation at these concentrations of 5-HT are, respectively, 170% and 307% above the endogenous or basal production rate of 2.7±0.3picomoles/minute/milligram of synaptosomal membrane protein. We have also been able to identify distinct types (Type #1, #2, #3, and #4) of high affinity, specific binding sites for 5-HT on isolated synaptosomal membranes from rat brain. Dissociation constants of 2.6 × 10?10M, 2.5 × 10?9M, 7.0 × 10?9M, and 4.6 × 10?8M, characterize the binding of 5-HT to our sites of Type #1 through Type #4 respectively. The specific, high affinity binding was saturated at 5-HT concentrations of 5 × 10?10M for the Type #1 sites, 5 × 10?9M for our Type #2 sites, 1 × 10?8M for our Type #3 sites, and 7 × 10?8M for our Type #4 sites. The 5-HT concentrations producing saturation of our specific binding sites of Type #1 and Type #4 are virtually identical to those that elicit the two maxima of 5-HT stimulated cyclic GMP production, indicating that a membrane-bound guanylase cyclase may be closely associated with certain 5-HT receptors and/or re-uptake sites. |
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Keywords: | Address reprint requests to: Dr. Elizabeth S. Quayle Neurosciences Program University of Alabama in B'ham University Station Birmingham Alabama 35294 USA. |
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