Physiological agonist-concentrations

18 June 2004

Indu S. Ambudkar

I think each agonist has to be examined within the context of

(i) how/where the cell "senses" it and

(ii) cell type.

Thus, there could be quite a difference between the effective "concentrations" of truly endocrine signals vs paracrine or neurocrine signals. Definitely some tissues such as salivary glands recieve their primary stimuli through neurotransmitter release near the cell. In fact, earlier EM has shown nerve endings in close proximity to the basolateral plasma membrane in salivary gland cells.

In these glands, there is a resting level of activity (stimulii unknown)and then a "regulated" level where fluid secretion increases 10-100 fold (in response to oral and sensory stimulii). We should go back and re-assess some of the old morphology as well as pharmacokinetic data.

My feeling is that the cells "custom design" each signaling pathway not only with regard to how (concentration, time, etc.) they recieve the signal but also which downstream function is regulated. In fact the latter might determine the former.

My suggestion is that we should stop generalizing our findings !!