Adenosine modulation of neuroeffector transmission in guinea-pig uterine smooth muscle

Abstract

Effects of adenosine and adenosine analogues on neuroeffector transmission in separate layers of the guinea-pig uterine smooth muscle during different phases of the oestrus cycle were studied. Adenosine (ADO), N6-[(R)-1-methyl-2-phenylethyl]- adenosine (R-PIA) and 5'-N-ethylcarboxamideadenosine (NECA) enhanced spontaneous contractile activity as well as contractile responses to nerve stimulation or direct muscle stimulation in the longitudinal and circular muscle layers both at the time of ovulation and implantation. The agonist potency order was R-PIA greater than or equal to NECA greater than ADO. Furthermore, in the circular muscle layer inhibitory effects were seen at time of implantation and the agonist potency for this inhibitory effect was NECA greater than R-PIA greater than or equal to ADO. 8-p-sulphophenyltheophylline (8-PSOT) antagonized both the stimulatory and inhibitory effects of the purines and 8-p-sulphophenyltheophylline applied to untreated preparations inhibited nerve-induced contractile activity. NECA inhibited stimulation-induced release of 3H in preparations incubated with [3H]noradrenaline. We suggest that adenosine and its analogues can modulate adrenergic neuroeffector transmission in guinea-pig uterine smooth muscle via action at postjunctional receptors stimulating contractile activity and prejunctional receptors inhibiting transmitter release. In the circular muscle layer postjunctional receptors inhibiting contractile activity were evident at time of implantation. Furthermore, endogenous purines exerting a stimulatory action on the neuroeffector transmission were likely formed during the present experimental conditions.