TY - JOUR
T1 - Rabbit cerebral cortex 5HT(1a) receptors
AU - Weber, John T.
AU - Hayataka, Kenneth
AU - O'Connor, Mary Frances
AU - Parker, Keith K.
N1 - Funding Information:
This work was supported by grants from the National Science Foundation, the Montana Science and Technology Alliance, the National Institutes of Health IDeA program, and the University of Montana. The technical assistance of Marta Morlan, Susan Wilson, Nancy Colson, Paul Brand, and Joseph Sure Chief was crucial in completing this work. Rabbit and rat brains were kindly donated by Bryan Tarr, Jerry Smith, Phil Bowman, Michael Minnick, and Craig Johnston. The advice of Rustem Medora in the parthenolide experiments is deeply appreciated.
PY - 1997/5
Y1 - 1997/5
N2 - Selective 5HT(1a) agonist binding to membranes from rabbit cerebral cortex was concentration-dependent and saturable; the Kd was 1.1 nM and Bmax of 480 fmols/mg protein. Scatchard as well as Hill plots were linear; the Hill coefficient was 0.96, suggesting a single, non-interacting binding site. Agonist binding was inhibited in a concentration-dependent fashion by gamma S GTP, a result consistent with the coupling of this binding site to the G protein signal transduction system. In competition experiments involving agonist and a series of agents with known affinities and specificities at 5HT(1a) receptors, a rank order relationship was found consistent with this binding site being a 5HT(1a) binding site. Direct comparisons of agonist and antagonist binding at rat cerebral cortex 5HT(1a) receptors and cloned human 5HT(1a) receptors also suggested that the rabbit binding site belongs to the 5HT(1a) class. The only rank order anomalies were with methiothepin in rabbit cerebral cortex, where a comparatively high Ki was observed and with buspirone in cloned human 5HT(1a) receptor, where a low Ki was determined; these anomalies bear further study in light of the comparative pharmacology of 5HT(1a) receptors. Finally, the natural product parthenolide was tested for affinity in the rabbit, rat, and human systems, where it uniformly was unable to displace agonist, suggesting that the 5HT(1a) receptor is not a target for this compound. Overall, these results suggest that a functional 5HT(1a) receptor exists in rabbit cerebral cortex.
AB - Selective 5HT(1a) agonist binding to membranes from rabbit cerebral cortex was concentration-dependent and saturable; the Kd was 1.1 nM and Bmax of 480 fmols/mg protein. Scatchard as well as Hill plots were linear; the Hill coefficient was 0.96, suggesting a single, non-interacting binding site. Agonist binding was inhibited in a concentration-dependent fashion by gamma S GTP, a result consistent with the coupling of this binding site to the G protein signal transduction system. In competition experiments involving agonist and a series of agents with known affinities and specificities at 5HT(1a) receptors, a rank order relationship was found consistent with this binding site being a 5HT(1a) binding site. Direct comparisons of agonist and antagonist binding at rat cerebral cortex 5HT(1a) receptors and cloned human 5HT(1a) receptors also suggested that the rabbit binding site belongs to the 5HT(1a) class. The only rank order anomalies were with methiothepin in rabbit cerebral cortex, where a comparatively high Ki was observed and with buspirone in cloned human 5HT(1a) receptor, where a low Ki was determined; these anomalies bear further study in light of the comparative pharmacology of 5HT(1a) receptors. Finally, the natural product parthenolide was tested for affinity in the rabbit, rat, and human systems, where it uniformly was unable to displace agonist, suggesting that the 5HT(1a) receptor is not a target for this compound. Overall, these results suggest that a functional 5HT(1a) receptor exists in rabbit cerebral cortex.
KW - 5HT(1a) receptor
KW - Buspirone
KW - Cloned human receptor
KW - G protein
KW - Methiothepin
KW - Parthenolide
KW - Rabbit cerebral cortex
KW - Rat cerebral cortex
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U2 - 10.1016/S0742-8413(97)00614-2
DO - 10.1016/S0742-8413(97)00614-2
M3 - Article
C2 - 9185324
AN - SCOPUS:0030975558
SN - 0742-8413
VL - 117
SP - 19
EP - 24
JO - Comparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology
JF - Comparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology
IS - 1
ER -