Effect on urinary bladder function and arterial blood pressure of the activation of putative purine receptors in brainstem areas.

The effect on bladder function and arterial blood pressure of adenosine-5'-triphosphate (ATP) and its synthetic analogue, alpha,beta-methylene ATP (alpha,beta-meATP) applied by microinjection to brainstem areas was assessed in the anaesthetised, paralysed and artificially ventilated female rat. Recordings of bladder pressure, changes in the pelvic nerve activity, arterial blood pressure and heart rate were evaluated. The purinergic drugs were microinjected into two brainstem areas the periaqueductal grey matter (PAG) and the area of the Barrington nucleus/locus coeruleus (LC) - only after electrical stimulation (50 Hz, 1 ms, 30-50 microA; n(PAG) = 17; n(LC) = 18) and the microinjection of glutamate (2 mM, pH 7.4+/-0.1; n(PAG) = 16; n(LC) = 16) had shown increases of bladder pressure and/or rate of bladder contractions and/or pelvic nerve activity at specific sites. Electrical and glutamate activation of PAG evoked an increase of arterial blood pressure. Microinjections of ATP (20 mM, pH 7.4+/-0.1; n(PAG) = 11; n(LC) = 11) and alpha,beta-meATP (2 mM, pH 7.4+/-0.1; n(PAG) = 10; n(LC) = 9) both evoked consistent increases of bladder pressure and/or pelvic nerve activity. Stimulation with ATP elicited a biphasic change of arterial blood pressure characterised by an increase followed by a decrease which was accompanied by a rise of heart rate. Microinjection of alpha,beta-meATP into PAG did not elicit a consistent response: a decrease of arterial blood pressure was evoked in five rats, while in two other rats an increase occurred. Electrical stimulation and glutamate activation of Barrington's nucleus/LC evoked an increase of arterial blood pressure, but a decrease was observed after microinjection of both ATP and alpha,beta-meATP. At some sites (n = 8) the effect of alpha,beta-meATP after a pre-injection at the same site of the P2 purino receptor antagonist, suramin (20 mM, pH 7.4+/-0.1) was smaller than the control. At three sites within PAG and two within LC located more medially to sites where an excitatory response had been observed, electrical stimulation evoked a small decrease or no change in bladder pressure. Following the stimulus, a rise in bladder pressure was preceded by an increase of pelvic nerve activity. A similar effect of glutamate was observed in one case. These data suggest that activation of P2 purine receptors in both PAG and Barrington's nucleus/LC is implicated in the neuronal mechanisms that generate patterns of activity in the parasympathetic innervation of the bladder and that purines also act at this level to modify sympathetic outflow to the cardiovascular system.