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alpha1B‐ and alpha2‐Adrenoceptors Mediate Contractions of Mouse and Rat Spleen; Pharmacological and Gene Knock‐out Data
Author(s) -
Docherty James,
Daly Craig
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.772.8
Subject(s) - prazosin , potency , antagonist , yohimbine , phenylephrine , endocrinology , medicine , agonist , spleen , chemistry , pharmacology , biology , receptor , in vitro , biochemistry , blood pressure
Contractions of rat spleen involve α1‐ and α2‐adrenoceptors, and α1‐ actions are probably mediated by α1B‐adrenoceptors (see Docherty, 2010). In the absence of a truly selective α1B‐adrenoceptor antagonist, it is difficult to positively identify the α1‐adrenoceptors involved. In this study, we have investigated norepinephrine (NE)‐evoked contractions of rat and mouse spleen employing pharmacology and knock‐out technology, α1A/D‐KO mice in which the only α1‐adrenoceptor remaining is the α1B‐adrenoceptor. Animals were killed by overdose of CO2 and cervical dislocation. In rat spleen, NE produced contractions with a potency (pEC50) of 5.43±0.06 (n=8, ‐log M), but NE was more potent in spleen from WT (7.04±0.08, n=6) and KO (7.14±0.05, n=4) mice. Prazosin (0.01 μM) or the α2‐adrenoceptor antagonist yohimbine (1 μM) produced only small shifts in NE potency, but the combination of praz and yoh produced 100 fold shift in NE potency in both rat and mouse. In rat spleen, the α1‐adrenoceptor agonist phenylephrine (PHE) produced contractions with a potency of 5.70±0.19 (n=6), and the putative α1B‐adrenoceptor antagonist cyclazosin (0.1 μM) significantly shifted PHE potency, but the selective α1D‐adrenoceptor antagonist BMY7378 (0.3 μM) was ineffective, and the α1A‐adrenoceptor antagonist RS100329 exhibited low potency. In α1A/D‐KO mice, the effects of praz and yoh were similar to their effects in WT mice. In spleen from both WT and KO mice, prazosin shifted the contractile response to higher concentrations of NE more markedly than the response to low concentrations. In conclusion, the major, if not exclusive, α1‐adrenoceptor involved in contractions of mouse, and probably rat, spleen is the α1B‐adrenoceptor. Dochery, J.R. (2010). Cell Mol Life Sci 67, 405‐417.