title: Heterogeneity of beta-adrenoceptors in guinea-pig brain: radioligand binding and cyclic nucleotide generation.
abstract: In this report, we have examined the radioligand binding and second messenger signalling characteristics of beta-adrenoceptors in the guinea-pig brain. [125I]-Iodocyanopindolol ([125I]ICYP)-labelled sites in the cerebellum and cerebral cortex were of similar densities (Bmax 34 and 24 fmol x mg(-1)) and affinities (K(D) 20 and 55 pM), respectively. Analysis of competition for [125I]ICYP binding in the cerebellum was compatible with the presence of a beta2-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 beta2-adrenoceptor. The [125I]ICYP binding profile in the cerebral cortex did not comply with those previously described for beta-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 beta2-adrenoceptor coupled to cyclic AMP generation, and potentiation of cyclic GMP accumulation. However, the guinea-pig cerebral cortex displays binding sites that exhibit beta-adrenoceptor-like pharmacology but fail to show functional coupling to cyclic AMP, cyclic GMP, or phosphoinositide signalling systems.
authors.affiliation: Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, England.
authors.forename: K E
authors.initials: KE
authors.lastname: Neil
authors.forename: F
authors.initials: F
authors.lastname: Hernández
authors.forename: D A
authors.initials: DA
authors.lastname: Kendall
authors.forename: S P
authors.initials: SP
authors.lastname: Alexander
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001667:Binding, Competitive / Q000502:physiology; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D006152:Cyclic GMP / Q000096:biosynthesis*; D005260:Female; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000096:biosynthesis; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011153:Population; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007295:Inositol Phosphates; D007457:Iodine Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); C026777:ICI 118551; D001262:Atenolol; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol; D000242:Cyclic AMP; D006152:Cyclic GMP; D000241:Adenosine; D007545:Isoproterenol