Capacitative Ca²⁺ entry through store-operated Ca²⁺ channels mainly contributes to activator Ca²⁺ for M₃-receptor-induced, LVOCC-independent tonic contraction of porcine coronary smooth muscle (CSM). Here, the signal transduction pathways involved in the M₃-receptor-mediated (270nM Ach) increase in isometric tension of CSM strips in the absence of L-VOCC-dependent Ca²⁺ influx were evaluated by means of specific inhibitors. RHC-80267 (30mM), an inhibitor of DAG-lipase markedly decreased the Ach-mediated contractile response by 81±3% (p<0.001), and 4-BPB (100mM), an inhibitor of PLA ₂, reduced it by 56±3% (p<0.001). Moreover, GF109203X (10mM), an inhibitor of PKC, nearly abolished the Ach-induced contractile response (91±6% inhibition; p<0.001). Likewise, the inhibitors of the arachidonic acid (AA) metabolism, 10mM indomethacin (COX inhibition) and 50mM NDGA (LOX inhibition), almost suppressed or strongly reduced the response by 90±4% (p<0.001) and by 40±3% (p<0.01). Conclusion: activation of PKC and production of AA metabolites are essential signaling steps in the L-VOCC-independent, M₃-receptor-mediated CSM tonic contraction, probably by sensitizing the contractile machinery to the small amount of activator Ca²⁺ delivered by store-operated Ca²⁺ channels. M₃-receptor-stimulation activates PLA₂ which besides DAG-lipase significantly contributes to the production of AA.