title: Alpha-2 adrenoceptors modulate the somatostatinergic system and G protein levels in the rat hippocampus.
abstract: alpha 2-Adrenoceptor agonists and somatostatin (SS) exert opposite effects on the spike discharge of pyramidal and granule cells in the rat hippocampus. We studied whether clonidine, an alpha 2-adrenoceptor agonist, and yohimbine, an alpha 2-adrenoceptor antagonist, can modulate somatostatin-like immunoreactivity (SSLI) levels, binding of 125I-Tyr11-somatostatin (125I-Tyr11-SS) to its specific receptors, SS-inhibited adenylyl cyclase (AC) activity, and the guanine-nucleotide binding regulatory proteins Gi and G(o) in the rat hippocampus. Clonidine (1 mg/kg, intraperitoneally (IP) or yohimbine (5 mg/kg, IP) injected at both 10 and 16 hours before decapitation did not affect SSLI content in the hippocampus. Clonidine administration decreased the number of specific SS receptors and increased the apparent affinity in hippocampal membranes. This change in SS binding was not the result of a direct effect of clonidine on these receptors because no effect in binding was produced by high concentrations of clonidine (10(-5) M) when added in vitro. Pretreatment with yohimbine prevented the clonidine-induced in SS binding. Yohimbine alone produced a significant increase in the number of 125I-Tyr11-SS receptors and a decrease in its apparent affinity. Clonidine decreased the ADP-ribosylation of a 41- and a 39-kDa G-protein by pertussis toxin (PTX), whereas yohimbine had no effect on the PTX-catalyzed ADP-ribosylation. No significant differences were seen for the basal or for the forskolin (FK)-stimulated AC enzyme activities in the control, clonidine- and/or yohimbine-treated groups. Somatostatin caused a significantly lower inhibition in AC activity in hippocampal membranes of clonidine-treated rats, whereas yohimbine led to an opposite effect.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Facultad de Medicina, Universidad de Alcalá, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: López-Sañudo
authors.forename: L
authors.initials: L
authors.lastname: Puebla
authors.forename: L G
authors.initials: LG
authors.lastname: Guijarro
authors.forename: J C
authors.initials: JC
authors.lastname: Prieto
authors.forename: E
authors.initials: E
authors.lastname: Arilla
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism / Q000502:physiology*; D013004:Somatostatin / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D018341:Receptors, Adrenergic, alpha-2; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015016:Yohimbine; D013004:Somatostatin; D000244:Adenosine Diphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D003000:Clonidine