INVOLVEMENT OF CAMP AND CGMP IN RELAXATION OF INTERNAL ANAL-SPHINCTERBY 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 (cA MP) and guanosine 3',5'-cyclic monophosphate (cGMP), in the opossum in ternal anal sphincter (IAS). The influence of the nonadrenergic noncho linergic (NANC) nerve stimulation (NS) by electrical field stimulation (EFS) and the putative neurotransmitters nitric oxide (NO) and vasoac tive intestinal peptide (VIP) on the above modalities was investigated . The fall in resting IAS tension in response to NS, NO, and VIP was a ccompanied by significant rises in both cGMP and cAMP. This fall and t he 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 cAM P and cGMP, respectively (P < 0.05). VIP (I X 10(-6) M) caused an 81.5 % fall of resting tension and 64.2 and 87.0% increases in cAMP and cGM P, respectively. Similarly, NO (1 X 10(-6) M) caused 69.6% fall in ten sion and an accompanying 93.4 and 415.9% rise of cAMP and cGMP, respec tively. Although EFS, VIP, and NO all lowered IAS tension and raised b oth cyclic nucleotides, the changes in cAMP and cGMP in the IAS are ot herwise stimulus specific, since fall in IAS tension by calcitonin gen e-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.