Involvement of cAMP and cGMP in relaxation of internal anal sphincter by neural stimulation, VIP, and NO.

We examined simultaneous changes in resting tension and tissue levels of the two second messengers, adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP), in the opossum internal anal sphincter (IAS). The influence of the nonadrenergic noncholinergic (NANC) nerve stimulation (NS) by electrical field stimulation (EFS) and the putative neurotransmitters nitric oxide (NO) and vasoactive intestinal peptide (VIP) on the above modalities was investigated. The fall in resting IAS tension in response to NS, NO, and VIP was accompanied by significant rises in both cGMP and cAMP. This fall and the levels of cAMP and cGMP were dependent on the intensity of EFS and the concentration of VIP and NO. EFS (2 Hz) caused a 63.5% fall of the resting tension with 61.7 and 118.2% rise of the tissue levels of cAMP and cGMP, respectively (P < 0.05). VIP (1 x 10(-6) M) caused an 81.5% fall of resting tension and 64.2 and 87.0% increases in cAMP and cGMP, respectively. Similarly, NO (1 x 10(-6) M) caused 69.6% fall in tension and an accompanying 93.4 and 415.9% rise of cAMP and cGMP, respectively. Although EFS, VIP, and NO all lowered IAS tension and raised both cyclic nucleotides, the changes in cAMP and cGMP in the IAS are otherwise stimulus specific, since fall in IAS tension by calcitonin gene-related peptide has been shown to be associated with an increase in cAMP without any change in cGMP, whereas the reverse was the case with atrial natriuretic factor. The common second messenger systems in IAS relaxation with NS, VIP, and NO suggest the involvement of VIP and NO as inhibitory neurotransmitters.