The present study was undertaken to clarify the effects of zinc ions (Zn2+) on Ca2+ uptake during histamine-induced contraction in guinea-pig taenia coli. Zn2+ (0.3 mM) had smaller effect on the initial phasic response to 10(-5) M histamine accompanied with decreased Ca uptake at the high affinity sites, while it inhibited the tonic response by inhibiting Ca2+ uptake at the low affinity sites. After the first stimulation with histamine in the presence of Zn2+ , the Ca2+ binding at high affinity sites was not significantly recovered in the presence of Zn-2 '. A second stimulation with histamine in the presence of Zn2+ did not elicit any phasic response. Furthermore, after beta -escin treatment of the fibres, which leaves receptor-coupled signal transduction including the Ca2+ storage sites intact, the contraction due to 10(-5) hi histamine was not so affected by 0.3 mM Zn2+, but, after resuspension in a solution of pCa 5, 10(-5) M histamine of second application did not elicit the contraction in the presence of Zn2+. These results suggested that Zn2+ does not affect the histamine-induced Ca2+ release from the intracellular storage sites in taenia coli. However, when Zn2+ is present, Ca2+ is not supplied to the storage sites for the phasic response due to second stimulation with histamine. In addition, Zn2+ reduced the tonic response to histamine mainly by inhibiting Ca2+ influx through receptor-operated and/or voltage-dependent Ca2+ channels. (C) 2000 Editions scientifiques et medicales Elsevier SRS.