The longitudinal muscle of guinea-pig ileum was used as a test tissue. Progressive (up to 70 min) treatment with phenoxybenzamine (10^-6 M) inhibited progressively the response to histamine and progressively decreased the density of histamine H₁-receptors. However, the 90 min treatment has no further significant inhibitory effect on the contractile response and did not decrease the density of the receptors. These results suggest that phenoxybenzamine discriminates between two distinct populations of H₁-receptors. Furthermore, it was found that the presence of GTP_γ-S made some populations of H₁-receptors resistant to phenoxybenzamine and facilitated an interaction of mepyramine with H₁-receptors.

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The effects of β-adrenoceptor stimulation by isoprenaline (ISO) on action potential and membrane current were studied in the guinea-pig was deferens in normal Krebs solution by using a double sucrose gap method.
In current-clamp experiments, ISO produced the membrane hyperpolarization by reducing the resistance and modified the pattern of multi-spike activity elicited by long depolarizing currents; an initial spike potential was reduced in the amplitude and the rate of rising phases and the slope of diastolic depolarization was slowered, leading to a prolongation of the spike discharge interval.
In voltage-clamp experiments, ISO greatly enhanced the late outward K⁺ current (I_K2) by increasing the conductance, but hardly affected the peak outward K⁺ current (I_K1). ISO also reduced the inward Ca²⁺ current (I_Ca) by decreasing the conductance (g_a) as well as by reducing the driving force for Ca²⁺. While it increased the leakage conductance (g₁) due to K⁺ associated with hyperpolarizing voltage steps.
In the preparations treated with Ca²⁺ channel blocker such as D-600, the enhanced effect of ISO on the I_K was still prominent, suggesting that Ca²⁺ and K⁺ channels appear to be independently regulated during β-adrenoceptor stimulation.
These results suggest that ISO exerts depressant actions on the was deferens muscle by reduction of the I_Ca as well as by prominent enhancement of the I_K2 via β-adrenoceptor activation.

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