Correlations of Purinergic, Cholinergic and Adrenergic Functions in Rabbit Corporal Cavernosal Tissue

Abstract

Erection involves cholinergic, adrenergic as well as non-cholinergic non-adrenergic nerves. Endothelial-derived relaxation factor plays an important role in mediating smooth muscle relaxation, which is crucial in initiating and maintaining erection. We previously showed that adenosine 5’-triphosphate (ATP) can induce significant relaxation in rabbit corporal cavernosal tissue. The present study presents effects of different neuron-transmitters and the role of endothelium in controlling the contractile/relaxant status of rabbit cavernosal tissue. These studies utilized isolated tissue strips prepared from the corpus cavernosum of sexually mature male New Zealand white rabbits. The results can be summarized as follows: (1) field stimulation caused relaxations with rebound contractions in most strips; (2) bethanechol (250 μM), isoproterenol (20 μM) and ATP (1 mM) all induced relaxations, though the relaxation induced by bethanechol was poorly sustained; (3) removal of the endothelium by rubbing decreased the relaxation to field stimulation and virtually eliminated the relaxation induced by bethanechol, but had no effect on the relaxation responses to isoproterenol and ATP; (4) methoxamine (200 μM) stimulated a sustained contraction of corporal cavernosal tissue, an effect unaltered by rubbing the strips; (5) low dose epinephrine induced relaxation, whereas higher concentrations contracted the tissue, and (6) β-adrenergic inhibition with propranolol (20 μM) was significantly more effective than mascarinic blockade with atropine (20 μM) in eliminating relaxation caused by field stimulation. Three conclusions can be drawn from this study: (l)ATP (purinergic innervation) may play an important role in erectile physiology, and its actions are independent of the endothelium, as well as cholinergic and adrenergic neurotransmission; (2) muscarinically induced cavernosal relaxation is endothelium-dependent, but constitutes a relatively minor portion of the relaxant response to electric stimulation, and (3) β-adrenergic stimulation constitutes a relatively prominent component of field stimulation-induced relaxation, and cavernosal β-adrenoceptors are more sensitive to low levels of adrenergic stimulation than α-adrenoceptors.

Activation of P2Y1 and P2Y2 nucleotide receptors by adenosine 5′-triphosphate analogues augmented nerve-mediated relaxation of human corpus cavernosum

“…On the other hand, others found that, in rabbit CCSM tissue, ATP played an important role in smooth-muscle relaxation, but its actions were independent of the endothelium. 7 Our previous data supported an independent NO-related mechanism. 17 Nevertheless, ATP enhanced the effect of the NO pathway, but appears not to be involved in activation.…”

“…6 Early studies in isolated corpus cavernosum smooth muscle Purinergic agonists augment nerve-mediated relaxation in HCC (CCSM) preparations demonstrated that ATP and other purines decreased both basal and phenylephrinestimulated tension. 7,8 Intracavernosal injection of ATP in dogs increased intracavernous pressures leading to penile erection. 9 Lee and coworkers 10 suggested that P2X receptors acted during the detumesence process.…”

Purinergic signalling in the reproductive system in health and disease

“…ATP can induce significant relaxations of rabbit cavernosal tissue which was unaffected by removal of the endothelium [402]. ATP has a powerful relaxant effect on corporal smooth muscle at high tone or pre-stimulated tissue, but causes contractions at low tone [443].…”

Corpus Cavernosum from Men with Vasculogenic Impotence Is Partially Resistant to Adenosine Relaxation due to Endothelial A2BReceptor Dysfunction

“…It is known that purinergic transmission is important for initiation and maintenance of penile erection (Tong et al, 1992). Due to its short half-life, adenosine has been used as an agent for the diagnosis of vasculogenic impotence (Kilic et al, 1994) without interfering with systemic blood pressure (Takahashi et al, 1992).…”