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Heterogeneity of β‐Adrenoceptors in Guinea‐Pig Brain: Radioligand Binding and Cyclic Nucleotide Generation
Author(s) -
Neil Karen E.,
Hernández Félix,
Kendall David A.,
Alexander Stephen P. H.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68062610.x
Subject(s) - isoprenaline , forskolin , medicine , cerebral cortex , radioligand , guinea pig , second messenger system , endocrinology , agonist , cerebellum , long term potentiation , chemistry , iodocyanopindolol , biology , stimulation , receptor , intrinsic activity
In this report, we have examined the radioligand binding and second messenger signalling characteristics of β‐adrenoceptors in the guinea‐pig brain. [ 125 I]lodocyanopindolol ([ 125 I]ICYP)‐labelled sites in the cerebellum and cerebral cortex were of similar densities ( B max 34 and 24 fmol·mg −1 ) and affinities ( K D 20 and 55 p M ), respectively. Analysis of competition for [ 125 I]ICYP binding in the cerebellum was compatible with the presence of a β 2 ‐adrenoceptor. In this tissue, isoprenaline evoked a cyclic AMP stimulation, and also potentiated cyclic GMP accumulations evoked in the presence of a nitric oxide donor, consistent with mediation via a β 2 ‐adrenoceptor. The [ 125 I]ICYP binding profile in the cerebral cortex did not comply with those previously described for β‐adrenoceptor subtypes, and isoprenaline failed to alter significantly cyclic AMP accumulation in the cerebral cortex, hippocampus, or neostriatum, even in the presence of forskolin or a phosphodiesterase inhibitor. Isoprenaline was also without effect on cyclic GMP accumulation or phosphoinositide turnover in the cerebral cortex. These results suggest that the guinea‐pig cerebellum expresses a functional β 2 ‐adrenoceptor coupled to cyclic AMP generation, and potentiation of cyclic GMP accumulation. However, the guinea‐pig cerebral cortex displays binding sites that exhibit β‐adrenoceptor‐like pharmacology but fail to show functional coupling to cyclic AMP, cyclic GMP, or phosphoinositide signalling systems.