Possible regulatory role of dynorphin A in the urinary bladder

Muscle strips from rat and human detrusor were studied using indirect immunofluorescence and electrical nerve stimulation in an organ bath. Immunoreactivity towards dynorphin was observed in varicose nerve fibres in the detrusor muscle and around immunonegative nerve cell bodies in the prevesical ganglia of the rat. In vitro, dynorphin A (1-13) (10(-13)-10(-6) M) strongly facilitated detrusor contraction induced by electrical field stimulation (EFS). This facilitation was counteracted by morphine (10(-10) and 10(-8) M) and naloxone (10(-10) and 10(-8) M) in a competitive manner. The facilitation could also be counteracted by the addition of the kappa-receptor antagonist M(r) 2266 (10(-7) M). Muscarinic blockade, achieved with atropine (10(-6) M), did not alter the effect of dynorphin A (1-13). Addition of phentolamine mesylate (10(-6) M), and propranolol (10(-6) M) per se facilitated the EFS-induced contractions. Both adrenergic blockade as well as the addition of the substance P blocker spantide, counteracted the facilitating effect of dynorphin A (1-13).

Dynorphin A immunoreactive material was found to be present in nerves in the rat detrusor and in prevesical ganglia. Dynorphin A (1-13) facilitated the detrusor contraction, possibly via actions on kappa-opioid receptors and interaction with non-cholinergic nerves.