β-Adrenoceptors have been demonstrated in the urinary bladders of many animals including the guinea pig. However, there is little information on the subtypes involved in the antispasmodic activity of β-adrenoceptor activation in the guinea-pig detrusor. The present study uses the non-selective β-agonist isoproterenol, the antagonist nadolol, the β₂-selective agonists salbutamol and terbutaline, the antagonist ICI 118551, and the β₁-selective antagonist metoprolol, to demonstrate functionally the subtypes existing in the guinea-pig detrusor. Isoproterenol dose-dependently reduces the myogenic activity in the guinea-pig detrusor induced by mild depolarization with 20 mM potassium in the tissue bath. At the supramaximal concentration of 30 µM, isoproterenol achieves 73 ± 2% of the reference maximal response. This activity of isoproterenol is reduced to 9 ± 5, 24 ± 6 and 54 ± 1 % in the total blockade of β, β₁ and β₂ with nadolol, metoprolol and ICI 118551, respectively. Consistently, salbutamol and terbutaline at the same concentration produce only 35 ± 1 and 38 ± 4% of the response, respectively. Thus, both β₁- and β₂-adrenoceptors are present in the detrusor of the guinea-pig urinary bladder. Although activation of either subtype results in antispasmodic action, the larger portion of the antispasmodic activity appears to be associated with the activation of the β₁-subtype.

The mechanoinhibitory effect of estradiol on the myogenic activity of guinea pig urinary bladder detrusor muscles was studied. In detrusor muscles tonically contracted with 80 mmol/l KCl, 17β-estradiol and the nonestrogenic isomer 17α-estradiol at 30 µmol/l reduced the contraction by 64 ± 3 and 59 ± 1 %, respectively. In detrusor muscles maintained in Ca²⁺-free media and depolarized with 80 mmol/l KCl, the contractile response of muscles to the reintroduction of Ca²⁺ was inhibited in a dose-dependent manner by 17β-estradiol, suggesting that 17β-estradiol blocked entry of extracellular Ca²⁺ into bladder smooth muscle cells and reduced the rise of intracellular Ca²⁺ required for contraction. In detrusor muscles mildly depolarized with 15 mmol/l KC1, 17β-estradiol reduced the myogenic activity with an IC₅₀ of 6.8 ± 1.3 µmol/l. The higher activity of 17β-estradiol in this latter test indicated that estradiol could also possess some K⁺ channel opening activity. Glibenclamide at 1 µmol/l did not affect the relaxant activity of 17β-estradiol in detrusor muscles stimulated with 15 mmol/l; however, this activity was diminished in a dose-dependent manner by iberiotoxin. Collectively, these results have demonstrated that in addition to the Ca²⁺ antagonist activity, 17β-estradiol possesses K⁺ channel opening activity in guinea pig urinary bladder smooth muscles, activating probably not the adenosine triphosphate sensitive, but the Ca²⁺-dependent large-conductance K⁺ channels.

No abstract

No abstract