α_1L‐Adrenoceptor mediation of smooth muscle contraction in rabbit bladder neck: a model for lower urinary tract tissues of man

Abstract

1 The a 1 -adrenoceptor population mediating contractile responses to noradrenaline (NA) in smooth muscles of the bladder neck from rabbit (RBN) has been characterized by use of quantitative receptor pharmacology. 2 Experiments with several`key' a 1 -adrenoceptor antagonists of varying subtype selectivities (RS-17053, BMY 7378, indoramin, 5-methylurapidil, prazosin, REC 15/2739, SNAP 5089, terazosin, WB 4101, tamsulosin, (+)-cyclazosin and RS-100329) were conducted. Schild regression analyses yielded a nity (mean pK b ) estimates of 7. 1, 6.2, 8.6, 8.6, 8.4, 9.3, 7.0, 7.4, 8.9, 10.0, 7.1 and 9.3, respectively, although deviations from unit Schild regression slope question the robustness of data for RS-17053 and SNAP 5089. 3 The nature of antagonism by these agents and the pro®le of a nity determinations generated together suggest that a single a 1 -adrenoceptor subtype mediates contractile responses of RBN to NA. Additional studies with phenylephrine indicated also an agonist-independence of this pro®le. Pharmacologically, this pro®le was reminiscent of that described as`a 1L '-adrenoceptor, which has been shown to mediate contractions of several tissues including lower urinary tract (LUT) tissues of man. Furthermore, a similarity was noticed between the`a 1L '-adrenoceptor described here in RBN and the rabbit and human cloned a 1a -adrenoceptor (based on data from both whole cell radioligand binding at 378C and [ 3 H]-inositol phosphates accumulation assays), characterizations of which have been published elsewhere. 4 In conclusion, the RBN appears to provide a predictive pharmacological assay for the study of NAinduced smooth muscle contraction in LUT tissues of man.

Role of the α-adrenergic system in femoral vascular reactivity in neonatal llamas and sheep: a comparative study between highland and lowland species

“…Having shown ex vivo differences in the α 1 -adrenergic-induced contraction and different prazosin affinities for these receptors, we then used RT-PCR to compare which of the α 1 -adrenergic receptors subtypes were present in the femoral arteries in both species. The data show a greater expression of α 1B -adrenergic receptor in newborn llama compared with newborn sheep, a finding consistent with a greater affinity for prazosin in newborn llamas ( 1 , 8 , 12 , 21 , 31 , 36 ).…”

Adrenoceptor Pharmacology: Urogenital Applications

“…Accordingly, NS-49, a selective α 1A -adrenoceptor agonist, produces selective increases in urethral pressure vis-a-vis systemic blood pressure when administered intravenously to the anesthetized dog [12]. However, as was observed for the prostate, unexpectedly low affinities for certain α 1A -adrenoceptor antagonists have also been observed in the urethra [13], and characterization of the contractile response to norepinephrine in the rabbit bladder neck also shows a pharmacological profile that would suggest the possible existence of the α 1L -adrenoceptor [14]. …”

Preclinical Pharmacology of α₁-Adrenoceptor Antagonists

“…Its tissue distribution and its functional role in normal and diseased tissue are still under investigation. Recently, the rabbit bladder neck has been proposed to represent a reliable pharmacological tool to study the effects of α 1 -adrenoceptor antagonists on α 1L -mediated contractions [10]. Table 2 summarizes the activities of six α 1 -adrenoceptor antagonists on phenylephrine contracted rabbit bladder neck (α 1L -mediated) or rat vas deferens (α 1A -mediated).…”