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The beat frequency of the myogenic heart of the tobacco hawkmoth, Manduca sexta, markedly increases at adult emergence in response to 2 blood-borne peptide neurohormones, known as the cardioacceleratory peptides (CAP1 and CAP2). Three independent lines of evidence are presented supporting the hypothesis that the CAPs exert their cardiostimulatory effects on the insect myocardium through a change in the intracellular levels of inositol 1,4,5-trisphosphate (InsP3). I show that (1) InsP3 levels increase in response to CAP2 in a timely fashion, (2) exogenous application of InsP3 mimics the effects of CAP2 application, and (3) a blocker of InsP3 metabolism inhibits the effect of CAP2. These results provide strong support for the hypothesis that InsP3 is likely to be the second messenger in the regulation of heart beat activity by CAP2. Besides establishing the nature of the signaling system between CAP2 and the heart, these data also identify a novel role for InsP3, namely, the control of contraction frequency in a myogenic muscle. Given the widespread distribution of cellular systems employing InsP3 as a second messenger, it is suggested that InsP3 may also be involved in the long-term regulation of rhythmic activity in other spontaneously contractile muscles and endogenously active cells.

Insect cardioactive neuropeptides: peptidergic modulation of the intrinsic rhythm of an insect heart is mediated by inositol 1,4,5- trisphosphate