EXCITATORY AND INHIBITORY ACTIONS OF NOREPINEPHRINE ON THE BA2-TYPE CA2+ CHANNELS OF SMOOTH-MUSCLE CELLS OF GUINEA-PIG VAS-DEFERENS( CURRENT THROUGH L)

The effect of norepinephrine (NE) was examined on the whole-cell Ba2current through L-type Ca2+ channels of freshly isolated smooth muscle cells of guinea-pig vas deferens. The magnitude of maximum Ba2+ curre nt [IBa(max)] varied in different cells, although the capacitance of t he cell membrane was similar (similar to 50 pF). Application of dbcAMP augmented IBa(max) by 37%, which was canceled by Rp-cAMPs, while PMA decreased the current by 32%, which was canceled by staurosporine. NE increased IBa(max) of the cells which originally showed relatively sma ll IBa(max), and decreased the current of the cells which showed large r IBa(max). In the presence of phentolamine, NE increased IBa(max), an d this effect was remarkable in cells showed smaller IBa(max). In the presence of propranolol, NE decreased IBa(max). The excitatory beta-ad renoceptor activation was canceled by Rp-cAMPs, and the inhibitory alp ha-adrenoceptor effect was canceled by staurosporine. It is suggested that NE shows dual (excitatory and inhibitory) actions on the L-type C a2+ channels of smooth muscle of guinea-pig vas deferens. The excitato ry beta-adrenoceptor action mediated through cAMP/PKA is predominant i n cells with lower density of the Ca2+ channels, while inhibitory alph a-adrenoceptor action mediated through PKC is predominant in cells wit h higher channel density. (C) 1996 Wiley-Liss, Inc.