Abstract
1. The mechanism of contraction to phenylephrine in the rat spleen (mediated via alpha 1B-adrenoceptors) has been studied in functional experiments. 2. The concentration-dependent contraction of the rat spleen to cumulative additions of phenylephrine (pD2 4.8 +/- 0.1) was not significantly reduced by the selective protein kinase C (PKC) inhibitor, calphostin C (10(-6)M) or potentiated by the DAG kinase inhibitor, R59022 (10(-6) M). 3. Contraction of the rat spleen in normal Krebs solution containing Ca2+ (2.5 mM) to a single concentration of phenylephrine (3 x 10(-4) M) produced a maximal response consisting of an initial phasic component and a more slowly developing tonic component. However in Ca(2+)-free Krebs solution (containing EGTA), phenylephrine (3 x 10(-4)M) produced only a phasic contraction which was reduced to 46 +/- 3% maximum response to phenylephrine in normal Krebs solution. 4. In some tissues after the contraction to phenylephrine (3 x 10(-4) M) in Ca(2+)-free Krebs solution (containing EGTA), the phenylephrine was washed out and the tissue was allowed to recover. After 2 h, upon addition of Ca2+ (2.5 mM) to the Krebs solution (EGTA now removed) a tonic contraction developed in the tissue (97 +/- 4% maximum response to phenylephrine). 5. Cyclopiazonic acid produced a tonic contraction of the rat spleen with a maximum effect at 10(-5) M (202 +/- 8% maximum response compared with that to phenylephrine). The contraction to CPA (10(-5) M) was reduced in Ca(2+)-free Krebs solution containing EGTA (30 +/- 4% of the maximum response to phenylephrine). One hour after the end of the contraction in Ca(2+)-free Krebs solution (EGTA now removed), upon addition of Ca2+ (2.5 mM) to the Krebs solution a tonic contraction developed in the tissue (263 +/- 12% maximum response to phenylephrine).(ABSTRACT TRUNCATED AT 250 WORDS)
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Selected References
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