Cyclic nucleotides in smooth muscle

Abstract

Publisher Summary Studies on the role of cyclic nucleotides, that is cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in smooth muscle relaxation began in the mid 1960s. If the role of cAMP (cyclic nucleotides) in smooth muscle relaxation appears to be relatively straight-forward, the role of cGMP (cyclic nucleotides) was less clear. The initial studies suggested a role for cGMP in mediating smooth muscle contraction. These conclusions were based on correlations between cGMP content and contraction in response to contractile agonists such as acetylcholine. A more thorough analysis, however, revealed that the elevations in cGMP observed with acetylcholine actually occurred after the onset of contraction, suggesting that cGMP was produced in response to intracellular Ca2+ elevations. It was not until the late 1970s that several investigators demonstrated that nitrogen oxide containing vasodilators such as nitroprusside and nitroglycerine elevated cGMP in smooth muscle tissues. These findings suggested that cGMP mediated relaxation of smooth muscle, a finding that was eventually supported by the discovery of the potent smooth muscle relaxing effects of cGMP analogs. Nevertheless, there have been dissociations reported between cyclic nucleotide elevating compounds or analogs on one hand, and the relaxation of different smooth muscle preparations on the other. Uterine smooth muscle relaxation, for example, is unaffected by elevations in cGMP. Vascular and bronchial smooth muscle, however, are highly responsive to the relaxing effects of cGMP. The diversity of responses to cyclic nucleotides in the various smooth muscle types may reflect different mechanisms that lead to the decrease in tone in the different types of smooth muscle.