Agonist-Induced Contraction and Accumulation of Inositol Phosphates in the Guinea-Pig Detrusor: Evidence that Muscarinic and Purinergic Receptors Raise Intracellullar Calcium by Different Mechanisms

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Abstract
In vitro contractile responses to electrical stimulation, ATP, histamine, and carbachol were measured in strips of guinea pig detrusor. The contractile responses were redetermined at intervals after replacement of the Krebs bicarbonate buffer with a nominally calcium-free medium. Agonist induced accumulation of [3H]-inositol phosphates was measured in a suspension of detrusor slices. Electrical stimulation (five second train; frequency 20 Hz; pulse width 100 .mu.s) produced a contraction that was abolished by retrodotoxin (10-6 M) and reduced by approximately 50% in the presence of atropine (10-8 M).This atropine resistant component was abolished by desensitization of the purine receptors with .alpha.,.beta.-methylene ATP, confirming that the response was mediated by nerves that released ATP and acetylcholine. Carbachol, ATP, and histamine produced concentration dependent contractions in guinea-pig detrusor strips. The response to ATP was much more dependent on extracellular calcium than the response to carbachol. Muscarinic, but not purine-receptor stimulation induced the accumulation of [3H]-inositol phosphates. These data suggest that ATP stimulates a purine receptor which opens a membrane ion channel and allows an influx of calcium while muscarinic receptor stimulation can mobilize intracellular calcium via hydrolysis of inositol phospholipid and production of the second messenger inositol triphosphate.