The capsular part of the central amygdala (CeC) is called the "nociceptive amygdala," as it receives nociceptive information from various pathways, including monosynaptic input from the lateral part of the parabrachial nucleus (LPB), a major target of ascending neurons in the spinal and medullary dorsal horn. LPB-CeC synaptic transmission is mediated by glutamate but the fibers from the LPB als...

In this retrospective, Dr. Lars Edvinsson recounts early steps and milestones in our understanding of the neuropeptide calcitonin gene-related peptide (CGRP) in the trigeminovascular system and its role in migraine. The discovery of the presence and function of CGRP and other neuropeptides in the cerebral vasculature and its sensory innervation is described. He relates the seminal finding that ...

We previously demonstrated that the neuronal expression of calcitonin gene-related peptide (CGRP), a potent vasodilator, is increased in deoxycorticosterone-salt-induced hypertension where it acts as a compensatory vasodilator to attenuate the elevated blood pressure. To determine whether CGRP is playing a similar role in subtotal nephrectomy-salt-induced hypertension, hypertension was induced ...

Deoxycorticosterone salt (DOC-salt) hypertension-induced renal damage is enhanced in α-calcitonin gene-related peptide (α-CGRP) knockout (KO) compared with wild-type (WT) mice. However, since the α-CGRP KO mice have a 15-20 mmHg higher baseline mean arterial pressure (MAP) than WT mice, they also have a higher MAP than WT mice throughout the course of DOC-salt hypertension. To determine the mec...

Responses to human CGRP, adrenomedullin (ADM), and proadrenomedullin NH2-terminal 20 peptide (PAMP) were studied in small human thymic arteries. CGRP, ADM, and PAMP produced concentration-dependent vasodilator responses in arteries preconstricted with the thromboxane mimic U-46619. Responses to ADM and PAMP were attenuated, whereas responses to CGRP were not altered by endothelial denudation. I...

We examined the effects of the calcitonin gene-related peptide (CGRP), including the possible participation of nitric oxide (NO), on mucin biosynthesis in the surface epithelium and remaining deep mucosa as well as the entire mucosa and compared the distribution of CGRP and NO synthase (NOS) using a combination of double immunofluorescence labeling and multiple dye filter. Pieces of tissue obta...

Peptide hormones and neuropeptides have important roles in physiology and therefore the regulation of these bioactive peptides is of great interest. In some cases proteolysis controls the concentrations and signaling of bioactive peptides, and the peptidases that mediate this biochemistry have proven to be extremely successful drug targets. Due to the lack of any general method to identify thes...

In the guinea pig distal colon, calcitonin gene-related peptide (CGRP, 0.1-30 nM) produced a concentration-dependent inhibition in electrically-evoked nonadrenergic noncholinergic (NANC) contractions and exogenous substance P-induced contractions. Both the inhibitory actions of CGRP were insensitive to human CGRP(8-37) (1-3 microM), a CGRP1 receptor antagonist. These results indicate that in th...

We investigated whether the sensory neuropeptide, calcitonin gene-related peptide (CGRP), could be synthesised by human lymphocytes. Our results indicate that in activated B-cells, there is a strong expression of CGRP gene transcripts, which is almost absent in resting cells. Since B-cells autocrinally produce NGF, the neutralisation of endogenous NGF by anti-NGF antibodies resulted in a marked...

Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. Activation and inhibition of CGRP receptors in the trigeminal ganglion may influence the activity...