Neurotransmitter or neuromodulator peptides that mediate withdrawal behavior such as pneumostome activity in the respiratory system (PubMed:11246168, PubMed:9622259, Ref.3). Possibly regulates calcium levels in command premotor interneurons (PubMed:11246168, Ref.3). Involved in neural modulation of the cardiovascular system, in addition to or as part of, the peptide's role in mediating withdrawal behavior (PubMed:9622259, PubMed:20399241). Appears to have a function in both the ventricle and auricle chambers of the heart; the effects are both positively inotrophic, by affecting the magnitude of ventricle contractions, and positively chronotropic, by affecting the frequency of auricle contractions (PubMed:20399241). In vitro modulates the spontaneous activity rate of parietal command neurons on motoneurons from the visceral ganglions that control pneumostome closure (PubMed:9622259). Likely to function as a neurotransmitter or neuromodulator that mediates withdrawal behavior. In vitro modulates the spontaneous activity rate of parietal command neurons on motoneurons from the visceral ganglion that control pneumostome closure. Involved in neural modulation that mediates pneumostome movements in the respiratory system as part of the withdrawal response (PubMed:16465488, PubMed:9622259). In vitro elicits an increase in the rhythmic activity of pneumostome motoneurons, and increases the frequency and intensity of pneumostome movements (PubMed:16465488, PubMed:9622259). This suggests that this peptide, and possibly other HCS2 peptides, may be responsible for the 'delayed effect' influence of the command interneurons which consists of an intensification of respiratory movements (PubMed:16465488, PubMed:9622259). Also promotes the growth of neuron processes in cultured cells extracted from the pleural ganglia, and may therefore have a role in development and/or rearrangements of the defensive neural network (PubMed:16465488). Occurs mainly on the granule surface (Ref.3). Present in the perikaryon of command neurons in the cytoplasm surrounding giant nuclei (Ref.3). Occurs mainly within the granule. Expressed in regions of the central nervous system that are known to control withdrawal behavior (PubMed:9622259, PubMed:11246168, PubMed:16465488, PubMed:16763780, Ref.3). Detected in the cell bodies and processes of the command interneurons (at protein level) (PubMed:16465488, PubMed:16763780, Ref.3). Predominately expressed in the LPa3/RPa3 and LW/RPa2 giant interneurons that are located in the parietal ganglia, as well as in other unidentified neurons in the pedal, pleural and cerebral ganglia (PubMed:9622259, PubMed:16763780, PubMed:11246168). Peptide CNP2: Detected in neural fibers that pass along the cardiorenal complex in the pericardium and arborize in adjacent connective tissue to innervate both the auricle, near the exit of the pulmonary vein, and the ventricle near the aorta (at protein level) (PubMed:20399241). The inner surface of the heart, ventricle neck region and aorta, are richly innervated with these neural fibers (at protein level) (PubMed:20399241). Also detected in large varicosities in the heart trabeculae and in the auriculoventricular region at the fiber terminals (at protein level) (PubMed:20399241). In the parieto-visceral ganglionic complex of the CNS, detected in a soma on the ventral caudal surface of the visceral ganglion and a soma located in the right parietal ganglion (at protein level) (PubMed:20399241). Peptide CNP3: Detected in the command interneurons (at protein level) (PubMed:16763780, Ref.3). Peptide CNP4: Detected in the cell bodies and processes of the command interneurons (at protein level) (PubMed:16465488, Ref.3). In embryos, not detected until 3 days before hatching when it is significantly expressed in the right but not in the left parietal giant interneurons. In juveniles under a month old, expression is higher in the right parietal giant interneurons compared to the left. In isolated central nervous system neurons, up-regulated or down-regulated in the cerebral, parietal, pleural and pedal ganglia in response to different stimuli. Up-regulated in response to noxious input such as injury, as well as by the application of neurotransmitters and second messengers such as serotonin that are known to be involved in withdrawal behavior. Also up-regulated by thapsigargin which increases the intracellular free calcium concentration. Down-regulated by a decrease in synaptic activity in the nervous system induced by increased Mg(2+) concentration.