Experimental evidence and dynamic aspects of spare receptor

Data obtained in radioligand - binding studies on guinea pig and mouse ileum were compared with those on the contractile responses to the muscarinic agonists methacholine (MCh), oxotremorine, bethanechol (BCh) and pilocarpine. Guinea pig ileum has a large amount of binding sites for 3 H-quinuclidinyl benzilate (QNB), a muscarinic antagonist, (102 fmoles/mg tissue), whereas mouse ileum has a small amount of these binding sites (19 fmoles/mg tissue). MCh, oxotremorine and BCh were full agonists in the contractile responses ofboth ilea, but pilocarpine was full agonist only in guinea pig ileum. After treatment with dibenamine (0.15 mM) (for 15 min at 30°C) guinea pig ileum exhibited maximal responses to MCh, oxotremorine and BCh, but not to pilocarpine, although the ED 50 values for the agonists in the muscle were increased by this treatment. The amount of binding sites of 3 H-QNB in dibenamine-treated guinea pig ileum was 55% of that in untreated ileum. When the amount of 3 H-QNB-binding sites in mouse ileum was decreased to 54% by dibenamine-treatment for 15 min, the maximal contractions induced by MCh, oxotremorine and BCh were also decreased to some degree. In low Ca 2+ medium, pilocarpine became a partial agonist in the contractile responses of guinea pig ileum. The following conclusions were drawn from these findings: 1. 1. The spare receptors proposed by Stephenson actually exist, and change in the amount of spare receptors, which can be brought about by dibenamine-treatment, or in low Ca 2+ medium, can change the ED 50 value of agonists. 2. 2. In a single tissue, the amount of spare receptors for different agonists differ, probably depending on the efficacy of the agonists. 3. 3. For a single agonist, the amount of spare receptors in a tissue differs from species to species, presumably depending on the total amounts of receptors.