Spare receptors
The term, spare receptors, or sometimes “receptor reserve”, refers to the proportion of the total population of receptors on a cell that are not required in order that an agonist is able to elicit a maximum response from the cell. For example, if an agonist need only activate 100 receptors to cause a cell to respond maximally, then in a cell with 2000 receptors, 1900 (95%) of those receptors would be spare since only 5% need to be bound by agonist to evoke a maximal response. The efficacy of the agonist is related to the proportion of receptors required by an agonist to evoke a maximal response, and agonists with a higher proportion of spare receptors have higher efficacy. The proportion of receptors which are spare is specific to a particular tissue and to a particular agonist – in other words, it is not a fixed number for a cell.
The same agonist described above would also elicit a maximal response in a cell type with 200 receptors expressed on the cell surface. However in that cell, only 50% of the receptors are spare, and the agonist would have lower efficacy in that tissue because it now needs to bind to 50% of the receptor population to elicit a maximal response.
In both of the above cases, the agonist would be a full agonist in the tissue, because it is able to elicit a maximal response from the cell. Consequently, any agonist with spare receptors in a particular cell type would be considered a full agonist in that cell or tissue. If the agonist described above was applied to a cell type expressing 100 receptors on the surface, it would still be able to elicit a maximum response by binding to 100% of the receptor population, and it would still be considered a full agonist, although there would now be no spare receptors present. However, in a different cell type expressing fewer than 100 receptors on the surface, or perhaps with a less efficient signal transduction system, this agonist would no longer be able to elicit a maximal response by binding to all of the receptors present. In that cell or tissue type, the agonist would be referred to as a partial agonist. Partial agonists do not have a population of spare receptors.
When identifying a drug as a partial agonist, it is important to clarify which tissue or organ is being referred to, since a drug can be a partial agonist in one tissue but a full agonist in another.
