European journal of pharmacology
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The mitogen-activated protein kinase (MAPK) family consists of the p42/p44 MAPKs and the stress-activated protein kinases, c-Jun N-terminal kinase (JNK) and p38 MAPK. We have previously reported that the human adenosine A(1) receptor stimulates p42/p44 MAPK in transfected Chinese hamster ovary cells. In this study, we have investigated whether the endogenous adenosine A(1) receptor in the smooth muscle cell line, DDT(1)MF-2 activates p42/p44 MAPK, JNK and p38 MAPK. ⋯ In contrast, wortmannin and LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), inhibitors of phosphatidylinositol 3-kinase, attenuated adenosine A(1) receptor stimulation of p42/p44 MAPK phosphorylation. In conclusion, the adenosine A(1) receptor stimulates p42/p44 MAPK through a pathway which appears to be independent of tyrosine kinase activation but involves phosphatidylinositol 3-kinase. Finally, adenosine A(1) receptor stimulation in DDT(1)MF-2 cells also activated p38 MAPK but not JNK via a pertussis toxin-sensitive pathway.
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Experiments were undertaken, using laser-Doppler flowmetry, to determine the nature of adrenoceptors mediating sympathetic nerve evoked nasal vasoconstrictor responses in anesthetized rats. Presence of sympathetic tone was confirmed by a large (330%) increase of nasal blood flow following section of the ipsilateral preganglionic cervical sympathetic nerve. Electrical nerve stimulation produced reproducible, frequency-related nasal vasoconstrictor responses with near maximal response, observed at less than 10 Hz. ⋯ Rats with intact cervical sympathetic nerves responded to rauwolscine with a modest constriction. Subsequent prazosin administration produced an increase of nasal blood flow of approximately 275%. These results suggest that the nasal vasculature of the rat is under intense sympathetic tone and that the resulting neurogenic vasoconstriction is mediated exclusively by activation of alpha(1)-adrenoceptors.