Hypothalamic cAMP and cGMP levels in ovariectomized rats were evaluated after intravenous (IV) pulse injection and/or intraventricular (IVT) injection of substance P and/or neurotensin. Intravenous substance P lowered hypothalamic cAMP concentration whereas IVT injection of 2.5 micrograms substance P produced significant increase in cAMP levels. On the other hand, IV administration of neurotensin failed to alter hypothalamic cAMP levels while IVT injection induced significant decrease in cAMP. Intravenous pulse injection of substance P elevated hypothalamic cGMP levels while IVT injection decreased cGMP concentration. Hypothalamic cGMP concentration was not modified by IV administration of neurotensin. However, IVT injection of neurotensin significantly elevated cGMP levels. Since a number of neurotransmitters/neuropeptides exert their action through cyclic nucleotides the present results indicate differential responses of cAMP and cGMP to substance P and neurotensin and implicate a mediatory role for cAMP and cGMP in the neuroendocrine action of substance P and neurotensin.
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