Muscle physiological role

Epinephrine itself does find some use in clinical medicine. The drug is used in order to increase blood pressure in cases of circulatory collapse, and to relax the bronchial muscle in acute asthma and in anaphylactic reactions. These activities follow directly from the agent s physiologic role. The biogenetic precursor of epinephrine, norepinephrine, has activity in its own right as a mediator of sympathetic nerve action. (An apocryphal story has it that the term nor is derived from a label seen on a bottle of a key primary amine in a laboratory in Germany N ohne... 

H. Kimura, Y. Nagai, K. Umemure, and Y. Kimura, Physiological roles of hydrogen sulfide synaptic modulation, neuroprotection, and smooth muscle relaxation. Antioxidants Redox Signaling 7, 795-803 (2005). 

In summary, in intact myometrium there is no clear physiological role for CICR despite the presence of RyR. This is the conclusion reached by others for a variety of smooth muscles e.g. taeniae coli (lino 1989), stomach (Guerrero et al 1994), tracheal myocytes (Fleischmann et al 1996) and portal vein (Kamishima McCarron 1996). 

Nelson MT, Quayle JM 1995 Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 268 C799—C822... 

The oft-touted argument against a physiological role for HbSNO is that even if it does form in RBCs, the Hb-bound NO has to make quite a journey to get to smooth muscle cells it must first cross the RBC plasma membrane, then the RBC free zone (Liao et al., 1999), then cross the endothelial cell membranes twice and finally go through the smooth muscle membrane. Why would nature adopt such a convoluted route when the endothelial cells next to the smooth muscle cells are producing membrane-diffusable NO ... 

In contrast to acetylcholinesterase, cholinesterase (acylcholine acyl-hydrolase, butyrylcholinesterase, EC 3.1.1.8) exhibits relatively unspecific esterase activity toward choline esters, with abroad specificity relative to the size of the acyl group. The enzyme is synthesized in the liver and can be found in smooth muscle, adipocytes, and plasma. Its physiological role remains partly obscure, but there is evidence that it is present transiently in the embryonic nervous system, where it is replaced in later stages of development by acetylcholinesterase. It has, therefore, been suggested that cholinesterase functions as an embryonic acetylcholinesterase. 

HT2 receptors are present on skeletal muscle membranes, but their physiologic role is not understood. Serotonin syndrome is a condition associated with skeletal muscle contractions and precipitated when MAO inhibitors are given with serotonin agonists, especially antidepressants of the selective serotonin reuptake inhibitor class (SSRIs see Chapter 30). Although the hyperthermia of serotonin syndrome results from excessive muscle contraction, serotonin syndrome is probably caused by a central nervous system effect of these drugs (Table 16-4 and Serotonin Syndrome and Similar Syndromes). 

The CNS contains a substantial amount of nitric oxide synthase (NOS), which is found within certain classes of neurons. This neuronal NOS is an enzyme activated by calcium-calmodulin, and activation of NMDA receptors, which increases intracellular calcium, results in the generation of nitric oxide. Although a physiologic role for nitric oxide has been clearly established for vascular smooth muscle, its role in synaptic transmission and synaptic plasticity remains controversial. Perhaps the strongest case for a role of nitric oxide in neuronal signaling in the CNS is for long-term depression of synaptic transmission in the cerebellum. 

A second GABA receptor subtype, the GABA-B receptor (Fig. 8—12) is not allo-sterically modulated by benzodiazepines but binds selectively to the muscle relaxant baclofen. Its physiological role is not well known yet, but does not appear to be closely linked to anxiety disorders or to anxiolytics. 

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