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Subtype-selective muscarinic antagonists effects on carbachol-induced and electric field-stimulated contractility of rat bladder were compared in vitro. Schild plot analysis of cumulative carbachol dose-response curves in the presence of antagonists was consistent with M3-mediated bladder contractions. However, nerve-evoked contractions were inhibited 15% at 30 Hz ( P < 0.01) by 10 nM pirenzepine (M1-selective antagonist), whereas 10 nM methoctramine (M2-selective antagonist) increased these contractions by 17% at 30 Hz ( P < 0.01). Identical doses had no effect on carbachol-induced contractions, indicating prejunctional M1 facilitory and M2 inhibitory receptors. m1 Receptors could not be identified by subtype-selective antibodies, nor could the m1 transcript be identified by Northern hybridization. However, m1, m2, m3, and m4 transcripts were identified in rat bladder using the reverse transcriptase-polymerase chain reaction, providing support for the existence of the m1 subtype. In conclusion, strong evidence is provided for the existence of prejunctional M1 facilitory and M2 inhibitory and postjunctional M3 receptors modulating contractility in the rat urinary bladder.

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The pressure-volume index (PVI) technique of bolus manipulation of cerebrospinal fluid (CSF) was used to measure changes of neural axis volume buffering-capacity and CSF dynamics produced by different conditions of the skull and dura. Twenty-eight cats were studied in the intact state, after bilateral craniectomy, and with the dura opened. At each stage of altering the container of the brain, the following parameters were obtained: steady-state intracranial pressure (ICP), sagittal sinus venous pressure, PVI, and the resistance to the absorption of CSF. The resistance to absorption of CSF was determined using both the bolus injection and the continuous infusion of fluid. After craniectomy, PVI increased from 0.76 +/- 0.04 to 1.3 +/- 0.07 ml (+/- standard error of the mean) (p less than 0.001) and increased further to 3.6 +/- 0.17 ml (p less than 0.001) after opening the dura. The resistance to absorption of CSF (Ro), determined by bolus injection, decreased after craniectomy from 91.3 +/- 7.5 to 56.3 +/- 6.2 mm Hg/ml/min (p less than 0.001) and decreased further to 8.9 +/- 0.66 mm Hg/ml/min (p less than 0.001) after opening the dura. Although resistance determined by constant infusion was similar, results were dependent on the rate of infusion. Despite these changes of resistance and PVI, steady-state ICP and sagittal sinus venous pressure were similar in all three conditions of the skull and dura. These studies indicate that changes of the container of the brain affect pressure-volume relationships within the neural axis. However, the changes of resistance to absorption of CSF are in a direction that preserves a steady-state hydrodynamic equilibrium.