ABSTRACT
The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C6) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50µM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250µM) decreased BC, increased MMP, but did not alter PMC-AUC. The effects of OXO-M on BC and PMC-AUC were suppressed by intravesical administration of AMN (50-100µM), and the effects of nicotine were blocked by hexamethonium (1mM). Antagonists infused intravesically alone did not alter reflex bladder activity. However, AMN (0.2mg/kg, subcutaneously) decreased PMC-AUC. 8-OH-DPAT (0.5mg/kg, s.c.), a 5-HT1A receptor agonist, suppressed the OXO-M-induced decrease in BC but not the enhancement of PMC-AUC. These results indicate that activation of cholinergic receptors located near the lumenal surface of the bladder modulates two types of reflex bladder activity (i.e., micturition and pre-micturition contractions). The effects may be mediated by activation of receptors on suburothelial afferent nerves or receptors on urothelial cells which release transmitters that can in turn alter afferent excitability. The selective action of nicotine on BC, while OXO-M affects both BC and PMC-AUC, suggests that micturition reflexes and PMCs are activated by different populations of afferent nerves. The selective suppression of the OXO-M effect on BC by 8-OH-DPAT without altering the effect on PMCs supports this hypothesis. The failure of intravesical administration of either AMN or hexamethonium alone to alter bladder activity indicates that cholinergic receptors located near the lumenal surface do not tonically regulate bladder reflex mechanisms in the SCI cat.
Subject(s)
Receptors, Cholinergic/metabolism , Reflex/physiology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Urinary Bladder/physiopathology , Urination/physiology , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Animals , Cats , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Muscarinic Agonists/pharmacology , Muscle Contraction/drug effects , Muscle Contraction/physiology , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Oxotremorine/pharmacology , Reflex/drug effects , Serotonin Receptor Agonists/pharmacology , Urinary Bladder/drug effects , Urination/drug effectsABSTRACT
The effects of 8-OH-DPAT (5-HT1A receptor agonist) and WAY100635 (5-HT1A receptor antagonist) on reflex bladder activity were investigated in alpha-chloralose anesthetized or conscious chronic spinal cord injured cats. The results were similar in both anesthetized and conscious animals. Cystometrograms revealed that 8-OH-DPAT (0.5 mg/kg, s.c.) significantly increased the bladder volume threshold for eliciting a large amplitude micturition contraction, but only slightly reduced the amplitude of the contractions and did not alter the small amplitude pre-micturition contractions. 8-OH-DPAT also reduced the amplitude of isovolumetric bladder contractions. The inhibitory effect of 8-OH-DPAT was reversed by WAY100635 (0.5 mg/kg) or blocked by pre-treatment with WAY100635. Reflex bladder contractions evoked by tactile stimulation of the perigenital region were not altered by 8-OH-DPAT. These results suggest that the inhibitory effect of 8-OH-DPAT is mediated by an action on interneuronal pathways in the spinal cord or on the C-fiber afferent limb of the spinal micturition reflex and not on bladder smooth muscle or the efferent limb of the reflex pathway. Drugs that activate 5-HT1A receptors might be useful in treating detrusor overactivity after spinal cord injury.
