Adrenergic receptors on smooth muscle cells isolated from human penile corpus cavernosum.
The effect of the alpha-adrenergic blocker moxisylyte was examined on smooth muscle cells isolated from human corpus cavernosum, and compared with that of other adrenergic agents and papaverine. Isolated smooth muscle cells were shown to contract (reduction of the mean cell length) under noradrenaline and carbachol stimulations in a time-dependent and concentration-dependent manner (maximum at 30 seconds, EC50 [noradrenaline] = 5 nM., EC50 [carbachol] = 1 nM.). The contractile effect of noradrenaline was dose-dependently inhibited by moxisylyte (IC50 = 0.5 +/- 0.2 microM.) and by prazosin (IC50 = 0.9 +/- 0.2 microM.). The dose-response curves were parallel and no statistically significant difference could be shown between the IC50 values. The alpha 2-adrenergic antagonist tolazoline also inhibited noradrenaline-induced contraction, whereas the alpha-adrenergic agonist methoxamine did not change the mean cell length. As expected, isoproterenol caused relaxation of noradrenaline-precontracted cells by interaction with a beta 2-adrenergic receptor. Papaverine was also found to inhibit the contraction induced by noradrenaline in a dose-dependent manner (IC50 = 2 +/- 0.3 nM.). Tritiated-dihydroergocryptine (3H-DHE) specific binding was competitively inhibited by moxisylyte and prazosin with the same IC50 value of 0.01 microM. Methoxamine and tolazoline also inhibited this binding with lower affinity (IC50 = 0.1 +/- 0.02 microM.), while isoproterenol did not change specific binding. Scatchard plots from saturation experiments with 3H-DHE and with 3H-N-methyl scopolamine revealed the presence of 15 times more adrenergic than muscarinic binding sites (650,000 and 45,000 sites per cell, respectively). Together, these data support evidence for the presence of postsynaptic alpha 1-adrenergic receptors on smooth muscle cells from human corpus cavernosum. These receptors are coupled with the contraction of the cell and are blocked by the alpha 1-adrenergic antagonists moxisylyte or prazosin. They also show that the phosphodiesterase inhibitor papaverine and the beta-adrenergic agonist isoproterenol induced relaxation. This model constitutes a new approach to study the potential targets of the adrenergic agents in the erectile tissue.
Service d'Urologie, C.H.U. Gaston Doumergue, Nimes and Faculté de Pharmacie, Montpellier, France.
P
P
Costa
M L
ML
Soulie-Vassal
B
B
Sarrazin
X
X
Rebillard
H
H
Navratil
J P
JP
Bali
D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D013948:Moxisylyte; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology*; D010413:Penis / Q000166:cytology*; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D013948:Moxisylyte