Re: Hexamethonium blocks cholinergic receptors.

Very good question.

It turns out that there are two major classes of receptors which are activated by acetylcholine (ACh). These two classes are different structurally as well as pharmacologically. One type is activated nicotine as well as ACh, and we refer to these as nicotinic acetylcholine receptors, or nAChRs. The second class is activated by muscarine, and we refer to them as muscarinic acetylcholine receptors, or mAChRs. These two broad classes have many subtypes within them (and in fact, I study one of those), but for our purposes here, they will suffice.

nAChRs are ligand-gated ion channels, meaning that when ACh binds to the receptor a channel in their center (referred to as an "intrinsic channel") opens. (This type of receptor is also called an ionotropic receptor.) Ions pass through this channel and depolarize the target cell. nAChRs are found throughout the nervous system and on skeletal muscle.

In contrast, mAChRs are G-protein coupled receptors, meaning that when ACh binds to the receptor a G-protein is activated. (This type of receptor is also called an metabotropic receptor.) The G-protein's activation causes a change in the metabolism of the cell and may open other types of ion channels or change gene transcription. mAChRs are found throughout the nervous system and on smooth muscle.

So, to answer your question, hexamethonium acts only on nAChRs and not on mAChRs. Since the effect of ACh on smooth muscle is mediated by mAChRs, hexamethonium has no effect.

Good references for this:

• Two types of cholinergic receptors -- the Cholinergic Pharmacology section of a medical school course at the University of Tasmania or the Neuromuscular section of the Washington University Medical School site. You can find some information on nAChRs on my nicotine and the nervous system site as well.
• Hexamethonium -- you can find more in the Merck Manual or you can look up specific references at PubMed at NIH.
• Since you are at a university, you can check in your library for books such as Principles of Neural Science by Kandel, Schwartz), and Jessell, Neurobiology by Gordon M. Shepherd, or The Biochemical Basis of Neuropharmacology by Cooper, Bloom, and Roth. You are likely to find other books on the same subject nearby.