Autonomic receptors in urinary tract: sex and age differences.

As age and sex affect the function of the lower urinary tract, we studied the characteristics of adrenergic and cholinergic receptors in various parts of lower urinary tract smooth muscle of young (6 months) and old (4 1/2-5 years) male and female rabbits. Saturation experiments performed with [3H]prazosin, [3H]yohimbine, [3H]dihydroalprenolol and [3H]quinuclidinyl benzylate in rabbit bladder base, bladder dome and urethra indicate the presence of regional, sex- and age-related differences in the density of alpha-1, alpha-2, and beta adrenergic and muscarinic cholinergic receptors. Alpha-2 adrenergic receptor density is considerably higher in the female than in the male urethra of both age groups, whereas the higher density of beta adrenergic receptors in the female than in the male bladder base is observed only in the younger animals. The density of muscarinic receptors is higher in bladder dome than in bladder base or urethra in young rabbits of both sexes. In the old animals, the density of muscarinic receptors in bladder base increases to the level observed in bladder dome. Inhibition experiments with selective adrenergic agonists and antagonists indicate that the pharmacological profiles of alpha-2 adrenergic receptors in the urethra and beta adrenergic receptors in the bladder dome and bladder base are similar in both sexes and at both ages. Beta-2 adrenergic receptors are shown to be predominant in bladder base and bladder dome of rabbits. Parallel studies in rabbit urethra, adult rat cortex and neonatal rat lung show that the urethral alpha-2 adrenergic receptors are of the alpha-2A subtype.

Characterization of autonomic receptors in neonatal urinary tract smooth muscle.

In the 1-day-old rabbit there are a large number of alpha-2- (labeled with [3H]yohimbine) than alpha-1- (labeled with [3H]prazosin) adrenergic receptors in the various parts of urinary tract smooth muscle, but the alpha-1 receptors are functionally more responsive to agonists than are the alpha-2 receptors. Unlike the findings in the adult rabbit, the neonatal bladder dome is functionally more sensitive to alpha-adrenergic agonists than the neonatal bladder base. The rank order of beta-adrenergic receptor densities (labeled with [3H]dihydroalprenolol) in various urinary tract smooth muscles correlates with the magnitude of the relaxant response to isoproterenol. There is a high number of functional muscarinic receptors (labeled with [3H]quinuclidinyl benzylate) in the neonatal urinary tract. The data demonstrate the existence of functional autonomic receptors in neonatal urinary tract smooth muscle.

Sex differences in function and distribution of alpha 1- and alpha 2-adrenoceptors in rabbit urethra.

To define the functional role of postsynaptic alpha-adrenoceptors in urethral smooth muscle, we examined the effects of various alpha-adrenergic agonists and antagonists on the contractile properties of the isolated urethra of male and female rabbits and quantified the population of alpha 1-and alpha 2-adrenoceptors, using radioligand receptor binding techniques. Norepinephrine (NE), epinephrine, and phenylephrine, an alpha 1-adrenergic agonist, induced increases in contractile force in both the male and female urethra. Clonidine, an alpha 2-adrenergic agonist, caused a relatively large contractile response in the female urethra but only a small contractile response in the male urethra. Receptor binding studies indicated that the male urethra contains almost equal amounts of alpha 1- and alpha 2-adrenoceptors (32 vs. 34 fmol/mg, respectively), whereas the female urethra contains a significantly greater density of alpha 2- than alpha 1-adrenoceptors (122 vs. 34 fmol/mg, respectively). Our studies indicate that both alpha 1- and alpha 2-adrenoceptors cause contractile responses in male and female rabbit urethra; and the greater response to alpha 2-agonist in female than male urethra is correlated with a higher density of alpha 2-adrenoceptors in this tissue.